More than half of the publishers listed alongside IntechOpen (18 out of 30) are Social Science and Humanities publishers. IntechOpen is an exception to this as a leader in not only Open Access content but Open Access content across all scientific disciplines, including Physical Sciences, Engineering and Technology, Health Sciences, Life Science, and Social Sciences and Humanities.
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Our breakdown of titles published demonstrates this with 47% PET, 31% HS, 18% LS, and 4% SSH books published.
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“Even though ItechOpen has shown the potential of sci-tech books using an OA approach,” other publishers “have shown little interest in OA books.”
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Additionally, each book published by IntechOpen contains original content and research findings.
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We are honored to be among such prestigious publishers and we hope to continue to spearhead that growth in our quest to promote Open Access as a true pioneer in OA book publishing.
Simba Information has released its Open Access Book Publishing 2020 - 2024 report and has again identified IntechOpen as the world’s largest Open Access book publisher by title count.
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Simba Information is a leading provider for market intelligence and forecasts in the media and publishing industry. The report, published every year, provides an overview and financial outlook for the global professional e-book publishing market.
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IntechOpen, De Gruyter, and Frontiers are the largest OA book publishers by title count, with IntechOpen coming in at first place with 5,101 OA books published, a good 1,782 titles ahead of the nearest competitor.
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Since the first Open Access Book Publishing report published in 2016, IntechOpen has held the top stop each year.
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More than half of the publishers listed alongside IntechOpen (18 out of 30) are Social Science and Humanities publishers. IntechOpen is an exception to this as a leader in not only Open Access content but Open Access content across all scientific disciplines, including Physical Sciences, Engineering and Technology, Health Sciences, Life Science, and Social Sciences and Humanities.
\n\n
Our breakdown of titles published demonstrates this with 47% PET, 31% HS, 18% LS, and 4% SSH books published.
\n\n
“Even though ItechOpen has shown the potential of sci-tech books using an OA approach,” other publishers “have shown little interest in OA books.”
\n\n
Additionally, each book published by IntechOpen contains original content and research findings.
\n\n
We are honored to be among such prestigious publishers and we hope to continue to spearhead that growth in our quest to promote Open Access as a true pioneer in OA book publishing.
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\n'}],latestNews:[{slug:"webinar-introduction-to-open-science-wednesday-18-may-1-pm-cest-20220518",title:"Webinar: Introduction to Open Science | Wednesday 18 May, 1 PM CEST"},{slug:"step-in-the-right-direction-intechopen-launches-a-portfolio-of-open-science-journals-20220414",title:"Step in the Right Direction: IntechOpen Launches a Portfolio of Open Science Journals"},{slug:"let-s-meet-at-london-book-fair-5-7-april-2022-olympia-london-20220321",title:"Let’s meet at London Book Fair, 5-7 April 2022, Olympia London"},{slug:"50-books-published-as-part-of-intechopen-and-knowledge-unlatched-ku-collaboration-20220316",title:"50 Books published as part of IntechOpen and Knowledge Unlatched (KU) Collaboration"},{slug:"intechopen-joins-the-united-nations-sustainable-development-goals-publishers-compact-20221702",title:"IntechOpen joins the United Nations Sustainable Development Goals Publishers Compact"},{slug:"intechopen-signs-exclusive-representation-agreement-with-lsr-libros-servicios-y-representaciones-s-a-de-c-v-20211123",title:"IntechOpen Signs Exclusive Representation Agreement with LSR Libros Servicios y Representaciones S.A. de C.V"},{slug:"intechopen-expands-partnership-with-research4life-20211110",title:"IntechOpen Expands Partnership with Research4Life"},{slug:"introducing-intechopen-book-series-a-new-publishing-format-for-oa-books-20210915",title:"Introducing IntechOpen Book Series - A New Publishing Format for OA Books"}]},book:{item:{type:"book",id:"8460",leadTitle:null,fullTitle:"Reproductive Biology and Technology in Animals",title:"Reproductive Biology and Technology in Animals",subtitle:null,reviewType:"peer-reviewed",abstract:"Reproductive success is a very important objective to ensure the evolution of animal species. In this sense, interesting research has been carried out to clarify various aspects of reproduction in different animal species. In this way, recent advances in the knowledge of reproductive biology and biotechnology developed for both males and females have been key to improving efficiency in different aspects. Thus, advances in the knowledge of sperm handling, oocyte characteristics, different genomic aspects related to somatic cell nuclear transfer, and the reproductive microarchitecture system in sheep, cows, pigs, and other invertebrates such as gastropods and fish are presented in this book. Additionally, we also present the most relevant topics of each area, making a detailed review of the knowledge reported to date.",isbn:"978-1-78984-180-0",printIsbn:"978-1-78984-179-4",pdfIsbn:"978-1-78984-206-7",doi:"10.5772/intechopen.78834",price:119,priceEur:129,priceUsd:155,slug:"reproductive-biology-and-technology-in-animals",numberOfPages:144,isOpenForSubmission:!1,isInWos:null,isInBkci:!1,hash:"32ef5fe73998dd723d308225d756fa1e",bookSignature:"Juan Carlos Gardón Poggi and Katy Satué Ambrojo",publishedDate:"April 15th 2020",coverURL:"https://cdn.intechopen.com/books/images_new/8460.jpg",numberOfDownloads:5604,numberOfWosCitations:0,numberOfCrossrefCitations:4,numberOfCrossrefCitationsByBook:0,numberOfDimensionsCitations:6,numberOfDimensionsCitationsByBook:0,hasAltmetrics:0,numberOfTotalCitations:10,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"January 10th 2019",dateEndSecondStepPublish:"January 31st 2019",dateEndThirdStepPublish:"April 1st 2019",dateEndFourthStepPublish:"June 20th 2019",dateEndFifthStepPublish:"August 19th 2019",currentStepOfPublishingProcess:5,indexedIn:"1,2,3,4,5,6",editedByType:"Edited by",kuFlag:!1,featuredMarkup:null,editors:[{id:"251314",title:"Dr.",name:"Juan Carlos",middleName:null,surname:"Gardón",slug:"juan-carlos-gardon",fullName:"Juan Carlos Gardón",profilePictureURL:"https://mts.intechopen.com/storage/users/251314/images/system/251314.jpeg",biography:"Juan Carlos Gardón Poggi received University degree from the Faculty of Agrarian Science in Argentina, in 1983. Also he received Masters Degree and PhD from Córdoba University, Spain. He is currently a Professor at the Catholic University of Valencia San Vicente Mártir, at the Department of Medicine and Animal Surgery. He teaches diverse courses in the field of Animal Reproduction and he is the Director of the Veterinary Farm. He also participates in academic postgraduate activities at the Veterinary Faculty of Murcia University, Spain. His research areas include animal physiology, physiology and biotechnology of reproduction either in males or females, the study of gametes under in vitro conditions and the use of ultrasound as a complement to physiological studies and development of applied biotechnologies. Routinely, he supervises students preparing their doctoral, master thesis or final degree projects.",institutionString:"Catholic University of Valencia San Vicente Mártir, Spain",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"2",totalChapterViews:"0",totalEditedBooks:"1",institution:null}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,coeditorOne:{id:"125292",title:"Dr.",name:"Katy",middleName:null,surname:"Satué Ambrojo",slug:"katy-satue-ambrojo",fullName:"Katy Satué Ambrojo",profilePictureURL:"https://mts.intechopen.com/storage/users/125292/images/system/125292.jpeg",biography:"Katy Satué Ambrojo received her Veterinary Medicine degree, Master degree in Equine Technology and doctorate in Veterinary Medicine from the Faculty of Veterinary, CEU-Cardenal Herrera University in Valencia, Spain. She is a Full Professor at the Department of Medicine and Animal Surgery at the same University. She developed her research activity in the field of Endocrinology, Hematology, Biochemistry and Immunology of horses. She is a scientific reviewer of several international journals : American Journal of Obstetrics and Gynecology, Comparative Clinical Pathology, Veterinary Clinical Pathology, Journal of Equine Veterinary Science, Reproduction in Domestic Animals, Research Veterinary Science, Brazilian Journal of Medical and Biological Research, Livestock Production Science and Theriogenology. Since 2014, she has been the Head of the Clinical Analysis Laboratory of the Hospital Clínico Veterinario from the Faculty of Veterinary, CEU-Cardenal Herrera University.",institutionString:"CEU-Cardenal Herrera University",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"9",totalChapterViews:"0",totalEditedBooks:"0",institution:{name:"CEU Cardinal Herrera University",institutionURL:null,country:{name:"Spain"}}},coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"1379",title:"Theriogenology",slug:"animal-science-theriogenology"}],chapters:[{id:"68101",title:"Micro-architecture of the Female Reproductive System",doi:"10.5772/intechopen.88023",slug:"micro-architecture-of-the-female-reproductive-system",totalDownloads:714,totalCrossrefCites:1,totalDimensionsCites:1,hasAltmetrics:0,abstract:"The female reproductive system consists of the ovary, oviduct, uterus, and vagina. This chapter will discuss how these organs look like under the microscope and what types of ultrastructural tissues are present in it, how the shape and physiology of the tissues/cells change with the physiological activities including reproductive cycles, what type of alterations occurs in the ovary during ovulation and how its follicle and epithelium differ, and how the ovulation takes place. The chapter will also elaborate how the lining epithelium and the tract mucosa facilitate the fertilized ovum and conceptus. Also, the chapter is highlighting the architectural changes within the mucosa of the uterus during and after pregnancy and type of ovary and spermatozoa that is most suitable for fertilization.",signatures:"Arbab Sikandar and Muhammad Ali",downloadPdfUrl:"/chapter/pdf-download/68101",previewPdfUrl:"/chapter/pdf-preview/68101",authors:[{id:"210551",title:"Dr.",name:"Arbab",surname:"Sikandar",slug:"arbab-sikandar",fullName:"Arbab Sikandar"},{id:"291279",title:"Dr.",name:"Muhammad",surname:"Ali",slug:"muhammad-ali",fullName:"Muhammad Ali"}],corrections:null},{id:"68402",title:"Oocyte Meiotic Resumption under High Surveillance",doi:"10.5772/intechopen.88291",slug:"oocyte-meiotic-resumption-under-high-surveillance",totalDownloads:661,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Germinal vesicle breakdown (GVBD) is the hallmark of oocyte meiotic resumption. It occurs under minimal stimulation during in vitro maturation (IVM). Several factors have been described to be involved in the inhibition of oocyte meiotic resumption such as purine derivatives. This study was assessing whether adenosinergic and guanosinergic systems are functional and participating in the inhibition of oocyte maturation. The objectives of the present study were to evaluate the effect of two purines, adenosine (ADO) and guanosine (GUO), on in vitro oocyte meiotic resumption, cumulus cell expansion, and gap junction communication. Both ADO and GUO significantly inhibited GVBD oocytes. The inhibitory effect lasted 24 hours and was reversible for meiotic resumption and cumulus cell expansion. Both ADO and GUO increased gap junction communication in cumulus cells. Equine chorionic gonadotropin (eCG) and the adenylyl cyclase stimulator, forskolin (FK), were both supportive of ADO and GUO inhibitory effect. The results are suggesting both adenosinergic and guanosinergic systems efficient in inhibiting oocyte meiotic resumption. The use of these two systems as part of a pre-IVM culture period would be a novel strategy to explore in order to improve oocyte developmental competence.",signatures:"François J. Richard",downloadPdfUrl:"/chapter/pdf-download/68402",previewPdfUrl:"/chapter/pdf-preview/68402",authors:[{id:"293923",title:"Prof.",name:"Francois",surname:"Richard",slug:"francois-richard",fullName:"Francois Richard"}],corrections:null},{id:"71188",title:"Effect of Pre and Post Weaning Diet Quality on Puberty Age and Tail Measures in Kurdish Female Lambs",doi:"10.5772/intechopen.88647",slug:"effect-of-pre-and-post-weaning-diet-quality-on-puberty-age-and-tail-measures-in-kurdish-female-lambs",totalDownloads:775,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"To determine the value of pre and post weaning nutrition on puberty age, some hormonal concentrations and tail measures in ewe lambs, a total of 40 clinically health Kurdish female lambs (30±8.6 d and weighing 10.2±3.4 kg) were randomly allocated to one of two experimental diets in pre-weaning period: high quality diet (HQD, 2.50 Mcal ME/kg dry matter (DM) and 148 g CP/kg DM) or low quality diet (LQD, 2.02 Mcal ME/kg DM and 87 g CP/kg DM). At weaning, one half of lambs from each group was randomly separated and assigned to HQD or LQD. So there were four treatment groups in post-weaning period: H-H (HQD pre- and post-weaning); H-L (HQD pre-weaning and LQD post-weaning); L-H (LQD pre-weaning and HQD post-weaning) and L-L (LQD pre and post-weaning, control group). Within the post-weaning, serum progesterone concentrations was greater for ewe lambs fed at H-H group than for other groups (P<0.05). Serum insulin concentration was affected by the diet quality at both periods (P<0.05). Leptin concentration was affected by treatment and ewe lambs of L-H group had higher leptin concentrations (P<0.05). Diet plan in the pre-pubertal period was affected tail measures in 120 and 210 days of ages (P<0.05).",signatures:"Sedigheh Menatian, Hamidreza Mirzaei Alamouti, Farshid Fatahnia and Reza Masoumi",downloadPdfUrl:"/chapter/pdf-download/71188",previewPdfUrl:"/chapter/pdf-preview/71188",authors:[{id:"297615",title:"Dr.",name:"Sedigheh",surname:"Menatian",slug:"sedigheh-menatian",fullName:"Sedigheh Menatian"}],corrections:null},{id:"70867",title:"Bioclimatic Influence on the Pregnancy Rate in Embryo-Recipient Cows in the Amazonian Biome",doi:"10.5772/intechopen.87998",slug:"bioclimatic-influence-on-the-pregnancy-rate-in-embryo-recipient-cows-in-the-amazonian-biome",totalDownloads:628,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"The objective of the research was to evaluate the effect of the climate, through the parameters of rectal temperature (RT), temperature and humidity index (THI), and plasma cortisol concentration, on the physiological responses of embryo-recipient cows in the Amazonian biome. For the conduction of the experiment in which 11 rural properties participated, 235 crossbred cows were used as embryo recipients. The embryos were obtained by means of the in vitro production technique (PIV). The recipients were divided into batches and submitted based on the simplification of the P36 protocol for fixed-time embryo transfer (FTET). To the day of embryo transfer, blood samples were collected by venipuncture of the coccygeal vein in tubes with anticoagulant. Plasma cortisol dosages were done by solid-phase radioimmunoassay (RIA) technique using commercial kits. The rectal temperature of each of the recipients submitted to the protocol was verified using a digital clinical thermometer, and the ambient temperature and the relative humidity of the air were evaluated in this moment, both with the aid of own digital equipment. Statistical analysis of the parameters evaluated was Pearson’s correlation and Student’s t-test at a significance level of 5%. In the analysis of variance, it was observed that there was a significant difference in plasma cortisol and THI among the groups, where lower mean values were found in the GP group. The Amazonian climate is an inducer of thermal stress, which can cause abnormalities in the estral cycle and changes in the synthesis of sex hormones and embryonic development and, consequently, negatively affect the pregnancy rate in embryo-recipient cows, even in races more adapted to the tropics, as demonstrated by the RT, THI, and plasma cortisol parameters.",signatures:"Jefferson Viana Alves Diniz, Laine Oliveira da Silva, Marina Marie Bento Nogueira, Rosano Ramos de Freitas, Marcos Nereu Luckner, Rafael Augusto Satrapa, José Antonio Dell’Aqua Junior and Eunice Oba",downloadPdfUrl:"/chapter/pdf-download/70867",previewPdfUrl:"/chapter/pdf-preview/70867",authors:[{id:"292338",title:"D.Sc.",name:"Jefferson",surname:"Diniz",slug:"jefferson-diniz",fullName:"Jefferson Diniz"},{id:"302276",title:"Dr.",name:"Rodolpho",surname:"Satrapa",slug:"rodolpho-satrapa",fullName:"Rodolpho Satrapa"},{id:"302277",title:"MSc.",name:"Rosano",surname:"De Freitas",slug:"rosano-de-freitas",fullName:"Rosano De Freitas"},{id:"302278",title:"MSc.",name:"Marcos",surname:"Luckner",slug:"marcos-luckner",fullName:"Marcos Luckner"},{id:"302280",title:"Dr.",name:"Rafael",surname:"Satrapa",slug:"rafael-satrapa",fullName:"Rafael Satrapa"},{id:"302283",title:"Prof.",name:"Euni",surname:"Oba",slug:"euni-oba",fullName:"Euni Oba"},{id:"302284",title:"MSc.",name:"Laine Oliveira",surname:"Da Silva",slug:"laine-oliveira-da-silva",fullName:"Laine Oliveira Da Silva"},{id:"302285",title:"MSc.",name:"Marina Bento",surname:"Nogueira",slug:"marina-bento-nogueira",fullName:"Marina Bento Nogueira"}],corrections:null},{id:"68240",title:"Recent Advance in Genome Editing-Based Gene Modification in Pigs",doi:"10.5772/intechopen.88022",slug:"recent-advance-in-genome-editing-based-gene-modification-in-pigs",totalDownloads:1143,totalCrossrefCites:1,totalDimensionsCites:2,hasAltmetrics:0,abstract:"Recently, a series of genome editing technologies including ZFNs, TALENs, and CRISPR/Cas9 systems have enabled gene modification in the endogenous target genes of various organisms including pigs, which are important for agricultural and biomedical research. Owing to its simple application for gene knockout and ease of use, the CRISPR/Cas9 is now in common use worldwide. The most important aspect of this process is the selection of the method used to deliver genome editing components to embryos. In earlier stages, zygote microinjection of these components [single guide RNA (sgRNA) + DNA/mRNA for Cas9] into the cytoplasm and/or nuclei of a zygote has been frequently employed. However, this method is always associated with the generation of mosaic embryos in which genome-edited and unedited cells are mixed together. To avoid this mosaic issue, in vitro electroporation of zygotes in the presence of sgRNA mixed with Cas9 protein, referred to as a ribonucleoprotein (RNP), is now in frequent use. This review provides a historical background of the production of genome-edited pigs and also presents current research concerning how genome editing is induced in somatic cell nuclear transfer-derived embryos that have been reconstituted with normal nuclei.",signatures:"Masahiro Sato, Kazuchika Miyoshi, Hiroaki Kawaguchi, Emi Inada, Issei Saitoh and Akihide Tanimoto",downloadPdfUrl:"/chapter/pdf-download/68240",previewPdfUrl:"/chapter/pdf-preview/68240",authors:[{id:"78725",title:"Dr.",name:"Kazuchika",surname:"Miyoshi",slug:"kazuchika-miyoshi",fullName:"Kazuchika Miyoshi"},{id:"177442",title:"Dr.",name:"Emi",surname:"Inada",slug:"emi-inada",fullName:"Emi Inada"},{id:"177443",title:"Dr.",name:"Issei",surname:"Saitoh",slug:"issei-saitoh",fullName:"Issei Saitoh"},{id:"245795",title:"Prof.",name:"Masahiro",surname:"Sato",slug:"masahiro-sato",fullName:"Masahiro Sato"},{id:"292466",title:"Dr.",name:"Hiroaki",surname:"Kawaguchi",slug:"hiroaki-kawaguchi",fullName:"Hiroaki Kawaguchi"},{id:"292467",title:"Prof.",name:"Akihide",surname:"Tanimoto",slug:"akihide-tanimoto",fullName:"Akihide Tanimoto"}],corrections:null},{id:"68489",title:"A Review of the Macroscopic, Microscopic, and Ultramicroscopic Characteristics of Some Key Oocyte Developmental Processes in Fish Species",doi:"10.5772/intechopen.87967",slug:"a-review-of-the-macroscopic-microscopic-and-ultramicroscopic-characteristics-of-some-key-oocyte-deve",totalDownloads:859,totalCrossrefCites:2,totalDimensionsCites:3,hasAltmetrics:0,abstract:"Studies involving the reproductive biology of fish have several possibilities of approach, such as the understanding of gonadal development, oocyte development, and the reproductive cycle of the species. In addition, analyses of gonadal morphology can be made at macro-, micro-, and ultramicroscopic levels. This knowledge helps to define factors that determine the different stages of gonadal development, as well as the “triggers” that initiate the reproductive process. In females, the growth and maturation of the ovarian follicles depend on a carefully elaborated communication between the follicular cells and the oocyte and a precisely organized contractile system. Changes in these systems appear to be related to apoptotic cells. This extensive remodeling of gonadal tissue, due to cell proliferation and differentiation, promotes also changes in the extracellular matrix. With this in mind, we provide herein a complementary and in-depth information on cell-cell and cell-matrix interactions related to the process of oocyte development in fish species. This information, together with the existing structural and ultrastructural descriptions of ovaries of different species, will enable a better understanding of the reproductive processes for the group of fish.",signatures:"Mônica Cassel",downloadPdfUrl:"/chapter/pdf-download/68489",previewPdfUrl:"/chapter/pdf-preview/68489",authors:[{id:"291226",title:"Dr.",name:"Monica",surname:"Cassel",slug:"monica-cassel",fullName:"Monica Cassel"}],corrections:null},{id:"68086",title:"Reproductive Cycle of Hexaplex princeps (Broderip, 1833)",doi:"10.5772/intechopen.88074",slug:"reproductive-cycle-of-em-hexaplex-princeps-em-broderip-1833-",totalDownloads:824,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"During two annual periods, the reproductive cycle of the gastropod Hexaplex princeps from Puerto Ángel, Oaxaca, Mexico was studied through gonadal histology. Sex proportion for the collected individuals was not statistically different from parity although most of the time, the number of males was slightly larger than that of females, which only outnumbered males during the spawning season. The maturity stages established for females were: (1) initial oogenesis, (2) previtellogenic maturity, (3) vitellogenic maturity, (4) maturity, (5) spawning, and (6) resting; and for males: (1) initial spermatogenesis, (2) maturity, (3) spawning, (4) onset of the rest, and (5) resting. Monthly variations of maturation stages showed that H. princeps has an annual reproductive cycle with a long period of gonadal activity. The spawning season comprised from November (females) and December (males) to March, with activity peaks in January. From March to October (females) and from May to June (males), reproduction resting occurred. Spawning was related to high chlorophyll concentrations due to the upwelling processes resulting from the winds and to the cooler sea surface temperatures occurring from November to March. This study provides baseline information that may serve to establish measures for sustainable exploitation strategies and for future aquaculture implementation of this species.",signatures:"Verónica Mitsui Saito-Quezada, Esther Uría-Galicia, José Luis Gómez-Márquez, Ana Bertha Villaseñor-Martínez, Ma. De Lourdes Jiménez-Badillo and Isaías Hazarmabeth Salgado-Ugarte",downloadPdfUrl:"/chapter/pdf-download/68086",previewPdfUrl:"/chapter/pdf-preview/68086",authors:[{id:"291343",title:"Dr.",name:"Verónica Mitsui",surname:"Saito-Quezada",slug:"veronica-mitsui-saito-quezada",fullName:"Verónica Mitsui Saito-Quezada"},{id:"291344",title:"Dr.",name:"Isaías",surname:"Salgado-Ugarte",slug:"isaias-salgado-ugarte",fullName:"Isaías Salgado-Ugarte"},{id:"299456",title:"Prof.",name:"Esther",surname:"Uría-Galicia",slug:"esther-uria-galicia",fullName:"Esther Uría-Galicia"},{id:"299457",title:"Dr.",name:"José Luis",surname:"Gómez-Márquez",slug:"jose-luis-gomez-marquez",fullName:"José Luis Gómez-Márquez"},{id:"299458",title:"Dr.",name:"Ana Bertha",surname:"Villaseñor-Martínez",slug:"ana-bertha-villasenor-martinez",fullName:"Ana Bertha Villaseñor-Martínez"},{id:"299460",title:"Dr.",name:"Ma. De Lourdes",surname:"Jiménez-Badillo",slug:"ma.-de-lourdes-jimenez-badillo",fullName:"Ma. De Lourdes Jiménez-Badillo"}],corrections:null}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},subseries:{id:"28",series:{id:"13",title:"Veterinary Medicine and Science",issn:"2632-0517",editor:{id:"38652",title:"Prof.",name:"Rita",middleName:null,surname:"Payan-Carreira",slug:"rita-payan-carreira",fullName:"Rita Payan-Carreira",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRiFPQA0/Profile_Picture_1614601496313",biography:"Rita Payan Carreira earned her Veterinary Degree from the Faculty of Veterinary Medicine in Lisbon, Portugal, in 1985. She obtained her Ph.D. in Veterinary Sciences from the University of Trás-os-Montes e Alto Douro, Portugal. After almost 32 years of teaching at the University of Trás-os-Montes and Alto Douro, she recently moved to the University of Évora, Department of Veterinary Medicine, where she teaches in the field of Animal Reproduction and Clinics. Her primary research areas include the molecular markers of the endometrial cycle and the embryo–maternal interaction, including oxidative stress and the reproductive physiology and disorders of sexual development, besides the molecular determinants of male and female fertility. She often supervises students preparing their master's or doctoral theses. 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\r\n\tExpert systems are the branch of artificial intelligence dealing with utilizing human expertise for solving problems. They are defined as computer systems that are capable of solving problems in the same way as a human expert would do when they face the same problem. With the current stream of digital transportation and an enormous amount of interest in intelligent systems, they will be a potential area of research for providing better intelligence to systems. They will also motivate the researchers to generate systems with more and more expertise. In this book, a general introduction to expert systems will be provided after a brief introduction to Artificial Intelligence. Detailed information about Expert Systems will be defined concerning their basic features and architectures as well as main characteristics and basic differences from traditional computer systems. Various applications of expert systems will also be provided. Potential readers will find both theoretical progress as well as practical applications. They will find a great amount of information to ease their research and implementation of intelligent systems.
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He worked as a Chief Researcher at the Information Technologies Institute of Turkish Science and Technology Council (TUBITAK). He also served as the vice president of the Turkish Measurement and Placement Center of Turkey and as a member of the Executive Board in the TUBITAK Public Research Group.",coeditorOneBiosketch:null,coeditorTwoBiosketch:null,coeditorThreeBiosketch:null,coeditorFourBiosketch:null,coeditorFiveBiosketch:null,editors:[{id:"306974",title:"Prof.",name:"Ercan",middleName:null,surname:"Oztemel",slug:"ercan-oztemel",fullName:"Ercan Oztemel",profilePictureURL:"https://mts.intechopen.com/storage/users/306974/images/system/306974.png",biography:"Prof. Dr. Ercan Oztemel was born in 1962 in Elazig of Turkey. He graduated from the Department of Industrial Engineering, Sakarya Engineering Faculty of Istanbul Technical University in 1984. 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1. Introduction
Arsenic, As, belongs to the group of elements that are called metalloids. A metalloid is a chemical element that has properties of both metals and nonmetals. Arsenic is from all its features mostly recognized as a poison. Arsenic has a complex chemical behavior since it exists in four different oxidative states [1]. Depending on oxidative state and presence in environment, arsenic species exhibit different toxicity [2]. Arsenic species can be present in all types of environment and can originate from natural and anthropogenic sources [3]. Natural sources of arsenic are: rocks with incorporated arsenic compounds, activity of volcanoes and some biological processes. Anthropogenic sources are numerous, from mining to different types of production (pesticides, wood preservatives, and pigments). When the arsenic compounds reach groundwater, it is hard to distinguish the origin, both natural and anthropogenic arsenic species are released [3].
According to Science Direct, during the last decade, a significant number of scientific papers reporting the results from arsenic investigations are presented in Figure 1. The focus of these researches was the development and improvement of methods for arsenic detection, extraction, separation and removal.
Figure 1.
The number of publications with keyword arsenic, according to Science Direct.
The investigation of arsenic species and their behavior in various samples, especially in natural waters and environment is important for chemistry and environmental protection. The most common arsenic species are presented in Table 1
Depending on the oxido-reduction conditions, microbiological environment, arsenic species can be present in water in solution or in a precipitated form, and they can also adsorb or desorb from the existing precipitates [1, 2]. When arsenic species are soluble in water, they can be present in both inorganic and organic forms. For iAs species both As(III), arsenite, and As(V), arsenate, can be present. For oAs species, MMA and DMA are soluble forms of organic arsenic species. From the value of the chemical equilibrium constants for each molecular or ionic form of arsenic in water, the present species can be recognized [3]. When choosing and analyzing the most dominant form of arsenic in water, the most present is inorganic arsenic as As(V). If As(III) is present, there are two important things that need to be taken into account. As(III) is more poisonous (even at low concentrations) than As(V). Beside the severe toxic effect, As(III) is easily oxidized. In oxidized conditions, stable forms of arsenic are As(V), and MMA and DMA, from oAs species. Many water sources in the world containing high concentration of arsenic cause health problems or diseases such as cancer. The WHO provisional guideline value for arsenic in drinking water is 10 μg L−1 [4]. Water quality analysis usually do not include test on arsenic. Arsenic compounds are colorless and odorless.
Once the presence of arsenic is determined in water, the separation and removal is obligatory. Removal technologies that are efficient, but still need improvement include absorption, precipitation, different electrochemical processes, membrane and hybrid membrane processes [6, 7, 8, 9].
2. Arsenic in water
Arsenic enters the water through the dissolution of minerals, ores soil, sediments, water, living organisms and rocks containing high concentrations of arsenic. Drinking water from surface water bodies usually does not contain high concentrations of arsenic. Higher concentrations have only been found in the groundwater. Human activities influence and change the content of arsenic in nature. When using arsenic compounds for different purposes, there is a direct influence. There is also indirect influence that affects the mobility of arsenic from different natural sources. Organic arsenic compounds such as AsB, AsC, TETRA, TMAO, arsenosugars and arsenic-containing lipids are mainly found in marine organisms although some of these compounds have also been found in terrestrial species.
Despite the fact that iAs species are predominant in natural waters, the presence of oAs has also been reported. Even though the main analytical interest is to determine total arsenic in water, it is also important to develop the procedures for As species determination, separation, and removal. The distribution of i As and oAs species is a function of pH value of water [2].
The distribution of arsenic species vs. pH values of water is presented in Figure 2 [2].
Figure 2.
The distribution of iAs and oAs species as a function of pH values of water [2]. Copyright approved by publisher.
As(III) species: H3AsO3, H2AsO3−, HAsO32− and AsO33−, are stable under slightly reducing aqueous conditions. As(V) species: H3AsO4, H2AsO4−, HAsO42− and AsO43−, are stable in oxygenated waters [6]. Two valences of the same element, molecular (ortho, H3AsO3, H3AsO4 and meta forms, HAsO2, HAsO3) and ionic forms with different charges make the research of arsenic removal from water more challenging and indivisible of arsenic chemistry knowledge. Any arsenic removal technology strongly depends on the water conditions and the stability of arsenic forms in the water.
Bearing in mind the fact that arsenic occurs in water in molecular and ionic form depending on water pH, the main goal of many investigations is to select the most efficient exchanger, not only in terms of efficiency, but also in terms of applicability in the wide range of water pH values in real and environmentally friendly water treatment systems. In neutral conditions, As(V) species are completely in ionic form (H2AsO4− and HAsO42−), while As(III) is in molecular (H3AsO3 or HAsO2), as shown in Figure 2 [2].
3. Determination of arsenic and arsenic species in water
There are a variety of chemical methods from classical to contemporary analytical techniques that are used for determination of arsenic and arsenic species in water.
There has been several review articles on the speciation of arsenic in a variety of samples [10, 11, 12, 13, 14]. These reviews focus on (1) determination of total content of arsenic and (2) speciation analysis.
A review of contemporary methods for arsenic and arsenic species in water is presented in Table 2. The parameters, as detection limit, advantages and disadvantages are pointed out in order to have an insight into ability and application of available techniques.
Methodology
Detection
Detection limit (μg L−1)
Advantages
Disadvantage
Ref.
ICP-AES
Total arsenic
~30
Minimal sample volume; no sample pretreatment and short measurement time
Expensive; needs lot of knowledge for operating and interpretation of data
A review of contemporary methods for arsenic and arsenic species determination in water.
The total concentration of arsenic in drinking water (mostly traces of arsenic, level of μg L−1 or less) can be detected only by sophisticated analytical techniques as ICP-MS, GF-AAS and HG-AAS [3, 14]. For As speciation analysis, well-established methods that involve the coupling of separation techniques, such as HPLC with a sensitive detection system, that is, ICP-MS, are recommended, and they are mostly used [13].
Historically, colorimetric/spectrophotometric methods have been used to determine total arsenic concentration. Several commercial field kits have been based on Marsh and Gutzeit reaction. All As species in a sample reduce to As (arsenic mirror) or arsine, AsH3, (it passes on to an HgBr2-impregnated filter, turning it to yellow to brown color, depending on the amount of arsenic present). These tests are obvious, visible proofs for arsenic detection, and they are popular and useful in the field of forensic toxicology. The colorimetric methods are easy to use and inexpensive in terms of equipment and operator cost. They are useful for the semi-quantitative determination of high concentrations of arsenic in water. Spectrophotometric methods are based on conversion of arsenic to the colored compound such as molybdenum blue, or silver diethyldithiocarbamate [15, 16].
Electrochemical methods, particularly voltammetric methods, are affordable, sensitive and ease of fabrication, and they are noteworthy for arsenic determination. Much work has been done in this area [12]. The ASV methods using platinum and gold electrodes, and CSV method using a glassy-carbon electrode have very low detection limit for arsenic determination. Determination of total As is performed by reducing As(V) to As(III) using various chemicals, and the limits of detection achieved were in vicinity of 0.02 μg L−1. Also, arsenic in drinking water can be measured with Cu(II) by differential pulse cathodic stripping voltammetry (DPCSV) using hanging mercury drop electrode (HMDE) as working electrode and Ag/AgCl as reference electrode [12, 17, 18].
At present, for total As concentration determination, laboratories often prefer more sensitive methods such as AAS, AES, MS or AFS. Usually, the total concentration of arsenic needs to be determined, then the speciation analysis follows.
To perform speciation analysis properly, the best option is coupling of two analytical techniques. One technique is used for the separation of all chemical forms of arsenic that are present in water, and the other is used for the detection of these species. Besides coupling analytical techniques, there are necessary steps for complete analysis of arsenic. The first one is the extraction of arsenic, which has to be both mild and effective, at the same time. The second step is separation of various forms of arsenic species. The final step is the measuring step which gives the answer to the quantification of each present arsenic compound.
3.1. Sophisticated coupling technique
Analytical methods for determining different arsenic species have become increasingly important due to different toxicity and chemical behavior of various arsenic forms. Methods that involve the coupling of separation techniques, such as IC and HPLC with a sensitive detection system, such as ICP-MS, HG-AFS, HG-AAS and GF-AAS [3, 11, 13, 14, 19]. HPLC has been a preferred technique used for separation of arsenic compounds. Coupled with ICP-MS for determination, as HPLC-ICP-MS system it is a method of choice for separation and measurements all arsenic species in water. In addition, applying IC coupled with ICP-MS, it is possible to separate and estimate arsenic species in water: iAs(III), iAs(V), DMA, MMA, AsBet. A representative result is presented in Figure 3 [19].
Figure 3.
Determination of five arsenic species by IC-ICP-MS. Mobile phase: NaOH [19].
The evaluation of analytical method is based on defining: selectivity, repeatability, accuracy, specific features of the method and defining the limits of detection and quantification (LoD and LoQ). These limits, these numbers give the information on the smallest concentration that can be detected and quantified with certain accuracy that has been defined [10]. The LoD was discussed and determined for the induced coupled plasma-mass spectrometry (ICP-MS) measurements of arsenic [11]. Thorough analysis has shown that the best option for LoD would be experiments, which would include the repetition many times. If experiments would be repeated 100 times, it is expected that only five measurements would be inadequate. Although this is ideal, the time consumption for the repetitive measurements is not acceptable. The most important conclusions were that LoD is not permanent and constant value, and it has to be verified and adopted for each new case. LoD is a basic parameter for estimation of the LoQ. It was concluded in [11] that the traditional (IUPAC) method is the one that could be applied.
4. Removal of arsenic and arsenic species from water
Different methods can be applied for arsenic removal from water. Arsenic (V) is more effectively removed than As(III) by both conventional and nonconventional methods. Pretreatmen (preoxidation) of As(III) to As(V) is an essential step for better removal [2]. Methods that have been successfully applied in water treatment plants are: precipitation and coprecipitation, electrochemical (such as electrocoagulation), ion exchange and MST (reverse osmosis, ultrafiltration and other membrane techniques) [6, 7, 8, 9, 20, 21].
4.1. Sorption processes for arsenic separation and removal
A wide range of sorbent materials for aqueous arsenic removal has been tested and used: biological materials, mineral oxides, activated carbons and polymer resins. Even some agricultural and industrial by-products such as red mud, fly ash, waste iron slag from steel production plant and waste filter sand from water treatment plant, have proved to be good and inexpensive arsenic sorbents [6, 7]. The potential use and application of industrial wastes in water treatment is in favor of the eco-friendly concept that preserves natural resources and supports the reuse-recycle concept. The technology of arsenic adsorption is based on materials which have a high affinity for dissolved arsenic. Adsorption of arsenic by iron modified sorbents has been established by several authors [6, 7]. There are numerous scientific and professional investigations with intention to develop a small and efficient system for arsenic removal based on natural and artificial sorption materials [20, 21]. Large amount of chemicals used for precipitation and coprecipitation processes (alum sulfate or ferric chloride) produce sludge, which needs treatment before disposal. If not treated properly, leachate with high concentration of arsenic is emitted to soil, threatening to contaminate the aquifers.
A step forward has been made by investigations that were devoted to the evaluation of selective multifunctional sorbents including ion-exchange resins for SPE and chromatographic columns connected with a sensitive measurements system [2]. The need to determine As species in water resulted in developing new materials for arsenic separation and removal. A simple procedure for selective separation (in pretreatment) of arsenic species in water using chemically modified and unmodified ion-exchange resins is presented in Figure 4 [2].
Figure 4.
Procedure for selective separation arsenic species in water using ion-exchange resins [2]. Copyright approved by publisher.
For separation of As species in water, two types of resins, strong base anion exchange resin (SBAE), hybrid resins (HY) and hybrid resin chemically modified (HY-Fe and HY-AgCl), were tested and used. The HY-Fe resin retained all arsenic species except DMAs(V). This is recognized as an advantage because this makes direct measurement of this species in the effluent possible. The HY-AgCl resin retained all iAs, which was convenient for direct determination of oAs species in the effluent. The selective bonding of arsenic species on three types of resins, as shown in Figure 4, has been established as the procedure which enables the separation and calculation of all arsenic species in water [2].
EC comprises complex chemical and physical processes involving many surface and interfacial phenomena. Very effective and perspective EC process consists of three processes: electrochemical reactions (simultaneous anodic oxidation and cathodic reduction), flotation and coagulation [9, 20]. The EC process relies on the generation of metal ions from electrodes. The electrodes can be made of iron, aluminum or zinc, depending on the most favorable reactions for arsenic removal. The reaction in reaction chamber starts after the application of direct current. The electrode (metallic anode) dissociates into valent metallic ions. The metallic ions migrate to oppositely charged ions and the precipitation of different insoluble salts occur (different sulfides, oxides, hydroxides, chromates or phosphates, depending on the presence of ions in water). EC has several advantages when compared to other methods. The construction of reaction chamber is compact, control of the process is simple, no additional chemicals are required, and the result is reduced amount of sludge. If the electrode is made of iron, ferric hydroxide is one of the main solid products, as shown in Eq. (1) [9]:
Fe3+aq+3OH−aq⇌FeOH3s.E1
Arsenate co-precipitates or adsorbs to Fe(OH)3(s), as shown in Eq. (2).
FeOH3s+AsO43−aq⇌FeOH3·AsO43−s.E2
The potential of EC as an alternative water treatment technique to remove arsenic from water needs to be realized [8, 9, 20].
Ion-exchange, IE, processes with regeneration capability is a proven, efficient and low-cost treatment method for the exchange of arsenic in the As(V) form [1, 2]. The ion-exchange reaction between As(V) and a bed of chloride-form SBAE resin (designated as R-Cl resin) occurs as presented by Eq. (3):
2R–Cl+HAsO42−⇌R2–HAsO4+2Cl−.E3
When the regeneration of resins is needed, both HCl and NaCl can be applied. Still, with HCl solution, more efficient regeneration occurs because the ionic forms of arsenic (anions) transform to molecular form (H3AsO4). Molecular forms do not affect the equilibrium of ion-exchange processes as illustrated by Eq. (4):
R2–HAsO4+2Cl−+2H+⇌2R–Cl+H3AsO4.E4
Different sorption processes, from adsorption, to chemisorption and ion-exchange, have shown a potential being efficient and cheap (depending on the selected sorbent). With improved, more selective and chemically modified sorbents, the extraction technique can be replaced [17, 18, 19]. What has been specifically used as an advantage for arsenic species separation is different behavior of arsenic species at various pH values [3, 22].
The hybrid resin (HY) that has successfully been applied uses the activity of the hydrated iron oxides (HFO) and anion exchange for selective separation of arsenic [2]. With integrated use of anion exchange and sorption, the separation of As(III) and As(V) species and removal of all species of arsenic can be accomplished. With application of HY resin, two separate things can be accomplished: the collection and preconcentration of low concentrated iAs or the removal of iAs species, if it is interfering the determination.
Membrane separation technologies, such as RO, NF, UF, MF, can be employed in the removal of arsenic from water. Depending on the removal efficiency, RO and NF are more efficient than UF and MF. Operating conditions, membrane material, water quality, temperature, pressure, pH value and chemical compatibility have to be considered during operation of a membrane plant. When MF and UF are applied, less amounts of chemicals are used, and therefore, less sludge is produced. When RO and NF are used, no chemicals are needed and the amount of sludge is neglectable [8].
The comparison and future perspective of different technologies for arsenic removal are presented in Table 3.
Technology for arsenic removal
Advantage
Disadvantage
Some specific feature
Future perspective
Adsorption
Cheap materials, effective and efficient removal
Further treatment for regeneration and consumption of chemicals
Additional filter for removal of fine particles is required
Still attractive as an efficient and cheap technology for As removal. Finding new, environmentally friendly sorbent is still a challenging task
Chemical coagulation
Effective for industrial wastewater treatment plants and efficient for As(V) removal
Chemical required. pH adjustment needed. Large volumes of sludge that needs further treatment
Arsenic leaching out from sludge
Not attractive as a solution, only if it coupled with electrochemical techniques
Electrocoagulation
Efficient for arsenic removal. Low maintenance costs. No chemicals or pH adjustment. Low operating costs
Applicable only on batch scale. Passive oxide films for on the electrode. High energy consumption
No generation of secondary pollutants
Attractive for future investigations. Need to overcome the lack of application on a large scale
Ion exchange
Efficient for As(V) removal. Exchange resins are available; the selective resins for removing arsenic are one of the most important requirements to provide high removal. Together with hybrid solution is an excellent technology
Interference with other ions. Easily blocked. Huge amount of chemicals
Using this kind of technique depends on the pH values of water
Attractive only if selective and sensitive chemical agents are included in ion-exchange process
Membrane technologies
Efficient in arsenic removal. No chemical reagents. No sludge. Small dimensions for membrane treatment plant. Easy automation and control
Removal of arsenic depends on the pressure, pH value, solute concentration, temperature of feed solution
Arsenic is concentrated in the retentate
Attractive in future perspective. With decrease of investment the MST will prevail in arsenic removal technologies. Different membrane materials and processes need to be evaluated to select the optimum for each situation
Table 3.
The comparison and future perspective of different technologies for arsenic removal.
5. Conclusion
Arsenic contamination of water has been reported as a critical issue in many articles, which reflects the latest state-of-the-art understanding of the behavior and toxicity of various arsenic species. Many water sources in the world contain low concentration of arsenic (mostly traces of arsenic, level of μg L−1 or less). If the concentration of arsenic in drinking water is higher than 10 μg L−1, which is the WHO provisional guideline value for arsenic, it causes various health problems. All arsenic compounds dissolved in water are toxic. In natural waters, arsenic appears most often in inorganic forms and to a lesser extent in organic form. Inorganic species, arsenic acids (H3AsO3 and H3AsO4) and their ions are more toxic than organic forms. In addition, As(III) species are more toxic than As(V) ones. The valence (+III and +V), the type of arsenic species, ionic or molecular forms are dependent on the oxidation–reduction condition and pH of the water. Arsenic in water occurs in both inorganic and organic forms, but inorganic species are predominant in natural waters. In neutral conditions, As(V) species are completely in ionic form (H2AsO4− and HAsO42−), while As(III) is in molecular form (H3AsO3 or HAsO2).
Arsenic compounds are colorless and odorless, and testing water for arsenic is an important strategy for the health and well-being of people. Working with a water professional to monitor and maintain the quality of the well and water supply is an important responsibility.
In this work, methods for arsenic and arsenic speciation separation, determination and removal were reviewed. There are numerous methods for separation and determination of arsenic species in water. It is very important to recognize easy, simple and inexpensive methods to estimate the very low concentrations of arsenic.
The total concentration of arsenic in drinking water can be detected by simple Gutzeit method, and some similar colorimetric methods of comparing stains produced on treated paper strips. Although its minimum detectable concentration is 1.0·μ L−1, these tests should be used when only a qualitative or semiqualitative detection is needed.
For precise, and reliable determination of arsenic in water, only sophisticated analytical techniques as ICP-MS, GF-AAS and HG-AAS can be applied. These methods are approved by US EPA. The features of these methods are high sensitivity, high accuracy, minimal sample volume; no sample pretreatment and short measurement time with minimum detectable concentration of 0.1 μ L−1. They are expensive, need lot of knowledge for operating and interpretation of data.
For As speciation analysis, well-established methods that involve the coupling of separation techniques, such as HPLC with a sensitive detection system, that is, ICP-MS, are recommended, and they are mostly used. Through the limits, it is possible to define the smallest concentration of analyte that can be reliably detected and quantified. Limit of detection for the HPLC-ICP-MS system is 0.001 μ L−1. This system is also expensive and needs lot of knowledge for operating and interpretation of data.
In all works, a special attention is paid to the preservation of arsenic species in environmental water samples for reliable speciation analysis. An appropriate procedure for the extraction of arsenic species from water should be accomplished without changing any original state of arsenic. This is still a challenging topic for research. The proposed system showed themselves to be accurate, precise and time efficient, as just a very simple sample treatment is required. Successful application of all methods required considerable practice.
Sorption processes (ion exchange, adsorption, chemisorption) with regeneration capability are proven as efficient and low-cost treatment methods for the removal of arsenic species from water. Separation of arsenic species using these new selective and chemically active sorbents recognize as a cost- and time-saving alternative to the traditional extraction techniques. The major drawback of all these techniques is that they are unable to remove As(III) efficiently.
Membrane separation technologies, such as RO, NF, UF, MF, are recommended for the removal of arsenic from water in water treatment plants.
Although there are numerous research papers focused on extraction techniques, yet it is not possible to set universal extraction procedures. These procedures depend on the presence of different species as well as on the type of matrices. For arsenic speciation, the choice of the most appropriate method is of great importance for obtaining reliable and accurate results.
Acknowledgments
The authors are grateful to the Ministry of Education and Science of the Republic of Serbia which supported our scientific work (projects no. TR37009, TR37010 and III43009).
\n',keywords:"arsenic, water, traces, species, toxicity, determination, removal, purification",chapterPDFUrl:"https://cdn.intechopen.com/pdfs/61143.pdf",chapterXML:"https://mts.intechopen.com/source/xml/61143.xml",downloadPdfUrl:"/chapter/pdf-download/61143",previewPdfUrl:"/chapter/pdf-preview/61143",totalDownloads:2086,totalViews:533,totalCrossrefCites:3,totalDimensionsCites:5,totalAltmetricsMentions:0,impactScore:2,impactScorePercentile:81,impactScoreQuartile:4,hasAltmetrics:0,dateSubmitted:"November 21st 2017",dateReviewed:"February 16th 2018",datePrePublished:null,datePublished:"July 25th 2018",dateFinished:"April 30th 2018",readingETA:"0",abstract:"Depending on the physical, chemical and biogeochemical processes and condition of the environment, various arsenic species can be present in water. Water soluble arsenic species existing in natural water are inorganic arsenic (iAs) and organic arsenic (oAs) species. All acidic species, according to the chemical equilibrium, have well-recognized molecular and ionic forms in water. The distribution of iAs and oAs species is a function of pH value of water traces of arsenic that are found in groundwater, lakes, rivers and ocean. The WHO provisional guideline value for arsenic in drinking water is 10 μg L−1. The most selective and sensitive methods for determination of total arsenic and its species in water are coupled techniques including chromatography, optical methods and mass spectrometry. Determination of arsenic species is of crucial importance for selection of arsenic removal technology. Best available technologies are based on absorption, precipitation, membrane and hybrid membrane processes. Adsorption is considered to be relatively simple, efficient and low-cost removal technique, especially convenient for application in rural areas. Sorbents for arsenic removal are biological materials, mineral oxides, activated carbons and polymer resins.",reviewType:"peer-reviewed",bibtexUrl:"/chapter/bibtex/61143",risUrl:"/chapter/ris/61143",book:{id:"6690",slug:"arsenic-analytical-and-toxicological-studies"},signatures:"Ljubinka Rajakovic and Vladana Rajakovic-Ognjanovic",authors:[{id:"141214",title:"Prof.",name:"Vladana",middleName:null,surname:"Rajakovic-Ognjanovic",fullName:"Vladana Rajakovic-Ognjanovic",slug:"vladana-rajakovic-ognjanovic",email:"vladana@grf.bg.ac.rs",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/141214/images/system/141214.jpg",institution:{name:"University of Belgrade",institutionURL:null,country:{name:"Serbia"}}},{id:"235766",title:"Prof.",name:"Ljubinka",middleName:null,surname:"Rajakovic",fullName:"Ljubinka Rajakovic",slug:"ljubinka-rajakovic",email:"ljubinka@tmf.bg.ac.rs",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:null}],sections:[{id:"sec_1",title:"1. Introduction",level:"1"},{id:"sec_2",title:"2. Arsenic in water",level:"1"},{id:"sec_3",title:"3. Determination of arsenic and arsenic species in water",level:"1"},{id:"sec_3_2",title:"3.1. Sophisticated coupling technique",level:"2"},{id:"sec_5",title:"4. Removal of arsenic and arsenic species from water",level:"1"},{id:"sec_5_2",title:"4.1. Sorption processes for arsenic separation and removal",level:"2"},{id:"sec_7",title:"5. Conclusion",level:"1"},{id:"sec_8",title:"Acknowledgments",level:"1"},{id:"sec_10",title:"Abbreviations",level:"1"}],chapterReferences:[{id:"B1",body:'Issa N, Rajaković-Ognjanović V, Jovanović B, Rajaković L. Determination of inorganic arsenic species in natural waters-Benefits of separation and preconcentration on ion exchange and hybrid resins. Analytica Chimica Acta. 2010;673(2):185-193. DOI: 10.1016/j.aca.2010.05.027'},{id:"B2",body:'Issa N, Rajaković-Ognjanović V, Marinković A, Rajaković L. Separation and determination of arsenic species in water by selective exchange and hybrid resins. Analytica Chimica Acta. 2011;706(1):191-198. DOI: 10.1016/j.aca.2011.08.015'},{id:"B3",body:'Rajaković L, Todorović Ž, Rajaković-Ognjanović V, Onjia A. Review: Analytical methods for arsenic speciation analysis. Journal of the Serbian Chemical Society. 2013;78:1-32. UDC JSCS-5666'},{id:"B4",body:'Guidelines for Drinking-Water Quality. Recommendations World Health Organization; WHO Press; Incorporating the First and Second Addenda. Vol. 1, 3rd ed. Geneva, Switzerland: World Health Organization; 2008'},{id:"B5",body:'Francesconi K, Kuehnelt D. Arsenic compounds in the environment. In: Frankenberger WT Jr, editor. Environmental Chemistry of Arsenic. New York: Marcel Dekker; 2002. pp. 51-94'},{id:"B6",body:'Lekić B, Marković D, Rajaković-Ognjanović V, Đukić A, Rajaković L. Arsenic removal from water using industrial by-products. Journal of Chemistry. 2013;2013:9 pages ID 121024. DOI: 10.1155/2013/121024'},{id:"B7",body:'Vukašinović-Pešić V, Rajaković-Ognjanović V, Blagojević N, Grudić V, Jovanović B, Rajaković L. Enhanced arsenic removal from water by activated red mud based on hydrated Iron(III) and titan(IV) oxides. Chemical Engineering Communications. 2012;199(7):849-864. DOI: 10.1080/00986445.2011.631235'},{id:"B8",body:'Uddin T, Mozumder S, Figoli A, Islam A, Drioli E. Arsenic removal by conventional and membrane technology: An overview. Indian Journal of Chemical Technology. 2007;14:441-450'},{id:"B9",body:'Song P, Yang Z, Zeng G, Yang X, Xu H, Wang L, Xu R, Xiong W, Ahmed K. Electrocoagulation treatment of arsenic in wastewaters: A comprehensive review. Chemical Engineering Journal. 2017;317:707-725. DOI: 10.1016/j.cej.2017.02.086'},{id:"B10",body:'Ariño C, Serrano N, Díaz-Cruz JM, Esteban M. Voltammetric determination of metal ions beyond mercury electrodes. A review. Analytica Chimica Acta. 2017;990:11-53. DOI: 10.1016/j.aca.2017.07.069'},{id:"B11",body:'Rajaković L, Marković D, Rajaković-Ognjanović V, Antanasijević D. Review: The approaches for estimation of limit of detection for ICP-MS trace analysis of arsenic. Talanta. 2012;102:79-87. DOI: 10.1016/j.talanta.2012.08.016'},{id:"B12",body:'Liu Z-G, Huang X-J. Voltammetric determination of inorganic arsenic (A review). Trends in Analytical Chemistry. 2014;60:25-35. DOI: 10.1016/j.trac.2014.04.0140165-9936'},{id:"B13",body:'Seulki J, Hosub L, Youn-Tae K, Hye-On Y. Development of a simultaneous analytical method to determine arsenic speciation using HPLC-ICP-MS: Arsenate, arsenite, monomethylarsonic acid, dimethylarsinic acid, dimethyldithioarsinic acid, and dimethylmonothioarsinic acid. Microchemical Journal. 2017;134:295-300. DOI: 10.1016/j.microc.2017.06.011'},{id:"B14",body:'Hung D, Nekrassova O, Compton R. Analytical methods for inorganic arsenic in water: A review. Talanta. 2004;64:269-277. DOI: 10.1016/j.talanta.2004.01.027'},{id:"B15",body:'Rupasinghea T, Cardwella TJ, Cattralla RW, Luquede MD, Spas C, Koleva D. Pervaporation-flow injection determination of arsenic based on hydride generation and the molybdenum blue reaction. Analytica Chimica Acta. 2001;445:229-238. DOI: 10.1016/S0003-2670(01)01256-9'},{id:"B16",body:'Gupta PK, Prabhat KG. Microdetermination of arsenic in water, spectrophotometrically, by arsine-silver diethyldithiocarbamate-morpholine-chloroform system. Microchemical Journal. 1986;33:243-251. DOI: 10.1016/0026-265X(86)90064-0'},{id:"B17",body:'Ma J, Sengupta MK, Yuan D, Dasguptab PK. Speciation and detection of arsenic in aqueous samples: A review of recent progress in non-atomic spectrometric methods. Analytica Chimica Acta. 2014;831:1-23. DOI: 10.1016/j.aca.2014.04.029'},{id:"B18",body:'Guo Z, Yang M, Huang X. Recent developments in electrochemical determination of arsenic. Current Opinion on Electrochemistry. 2017;3:130-136. DOI: 10.1016/j.coelec.2017.08.002'},{id:"B19",body:'Vassileva E, Becker A, Broekaert J. Determination of arsenic and selenium species in groundwater and soil extracts by ion chromatography coupled to inductively coupled plasma mass spectrometry. Analytica Chimica Acta. 2001;441:135-146. DOI: 10.1016/S0003-2670(01)01089-3'},{id:"B20",body:'Nidheesha P, Anantha Singh T. Arsenic removal by electrocoagulation process: Recent trends and removal mechanism. Chemosphere. 2017;181:418-432. DOI: 10.1016/j.chemosphere.2017.04.082'},{id:"B21",body:'Rajaković L, Mitrović M. Arsenic removal from water by chemisorption filters. Environmental Pollution. 1992;75(3):279-287. DOI: 10.1016/0269-7491(92)90128-W'},{id:"B22",body:'Syahidah N, Zulkifli H, Abdul R, Woei-Jye L. Detection of contaminants in water supply: A review on state-of-the-art monitoring technologies and their applications. Sensors and Actuators B: Chemical. 2018;255:2657-2689. DOI: 10.1016/j.snb.2017.09.078'}],footnotes:[],contributors:[{corresp:"yes",contributorFullName:"Ljubinka Rajakovic",address:"ljubinka@tmf.bg.ac.rs",affiliation:'
Faculty of Technology and Metallurgy, University of Belgrade, Serbia
Faculty of Civil Engineering, University of Belgrade, Serbia
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1. Introduction
The benzimidazole nucleus is fairly unique among heterocyclic ring systems because of its outstanding structural similarity with various naturally occurring nucleotides [1]. In 1872, Hoebrecker synthesized the first benzimidazole molecule by the reduction of 2-nitro-4-methylacetanilide [2]. The biological significance is because its structure is similar to purines, and the importance of the applications depends on their abundance in most of the biologically active molecules. The discovery of the structure of vitamin B12 with 5, 6-dimethylbenzimidazole moiety in it, also elicited the search for benzimidazole - similar motifs for various pharmacological applications [3, 4, 5]. Following this, various research groups have outlined the synthesis and applications of benzimidazole [6, 7]. Benzene when fused with imidazole results in the formation of benzimidazole (1), which can readily undergo tautomerization as shown in Figure 1.
Figure 1.
Benzimidazole (compound 1) with its tautomeric forms.
The greater reactivity of the 2nd position towards various electrophiles and nucleophiles is the outcome of tautomerization. Many drugs contain the benzimidazole nucleus as a core unit and have a widespread application in the pharmaceutical field [8, 9, 10, 11, 12, 13, 14]. The presence of benzimidazole pharmacophore in the various branches of medical science is inexplicable. The therapeutic uses of benzimidazole include anticancer [15, 16, 17, 18, 19, 20], antimicrobial [21, 22, 23, 24], antiparasitic [25, 26], anti-inflammatory and analgesics [27, 28, 29], antiviral [30, 31, 32], and antiulcerative [33] activities and in fields like ophthalmology, neurology, endocrinology, etc. The first example of a benzimidazole that was clinically available was thiabendazole (2), which can be used as a fungicide and for antiparasitic purposes [34]. The 2, 6-disubstituted albendazole (3) and mebendazole (4) were used as anthelmintic or antiparasitic agents. The 1, 2-disubstituted benomyl (5) was shown to have antifungal and anticancer activities whereas 2-substituted lansoprazole (6) acted as a therapeutic agent for the reduced production of stomach acid and cardiac failures (Figure 2).
Figure 2.
Drugs (compound 2, 3, 4, 5 and 6) based on benzimidazole core.
In this chapter, a plethora of benzimidazole analogs with different pharmacological properties such as anticancer, antibacterial, antifungal, antiviral, anticoagulant, anti-inflammatory, antiparasitic, anthelmintic activity, etc. has been discussed.
2. Benzimidazole and its pharmacological significance
Benzimidazoles were initially used as a plant fungicide and veterinary anthelminthic. After the discovery and use of thiabendazole (2), these benzimidazole motifs were used in human beings as well. Since then, a wide variety of molecules having the core structure as (1) were synthesized and found their application in the medical world as well as in the material domain.
Various substituted derivatives of (1) were showcased diversified therapeutic properties such as antiparasitic, anticancer, anthelmintic, antiproliferative, antioxidants, antimicrobials, anti-inflammatory, antivirals, anticoagulants, antihypertensive, anticonvulsant, antidiabetic, lipid level modulators, anti-HIV, immunomodulators, hormone modulators, proton pump inhibitors and antidepressants. They have also used a building block for various other therapeutic agents. Let us have a peep at some of the innumerable reports of pharmacological activities of benzimidazole.
2.1 Anticancer activity
Cytotoxicity of benzimidazole derivatives is well known and, recently Noha et al. reported compounds of benzimidazole which are N-(benzimidazothiazolone) acetamides (7) [35]. In vitro analyses provided the cytotoxic activity of (7) over HCT-116 colon cancer cells. The further detailed study delivered the topoisomerase I-β (Topo I-β) and inhibiting activities against tubulin (Figure 3).
Figure 3.
Benzimidazole derivatives (compound 7, 8, 9 and 10) acts as cytotoxic agents, chemosensors and repurposed drugs.
The role of benzimidazole analogs as potential metal-based DNA-sensor is unanimous. Fluorogenic differential/sequential Schiff base chemosensors which solely consists of benzimidazole derivatives (8), for detecting Cu2+, CN−, P2O74−, and Zn2+ ions in human cervical (HeLa) and breast cancer (MDA-MB-231 and MCF-7) cell lines were designed by Anbu et al. [36] (Figure 3).
Drug repurposing of benzimidazole compounds is generally considered for the reason that, it has antitumor activities. Florio and coworkers screened anthelmintics which are derivatives of benzimidazole [37]. Certain drugs like albendazole (3), flubendazole (9), oxibendazole (10) etc. are subjected to the evaluation of their pharmacokinetics and physicochemical properties (Figure 3). For the potential repurposing of the drugs in cancer therapy, a silico target prediction was used to access the pharmacology of these benzimidazole compounds.
Synthesis of N-substituted benzimidazole analogues (11–15) with an alkyl chain and a nitrogen-containing 5- or 6-membered ring increased the anticancer effects on human ovarian carcinoma (OVCAR-3) and human breast adenocarcinoma (MCF-7) cell lines, were reported by Hsieh et al. [38]. (2E)-1-(1-(3-morpholinopropyl)-1H-benzimidazol-2-yl)-3-phenyl-2-propen-1-one) (11) acts as the most potent antiproliferative drug and has got more advantages than the standard drug, cisplatin (Figure 4).
Figure 4.
N-substituted benzimidazole derivatives (compound 11, 12, 13, 14 and 15) with antiproliferative activity.
The stabilization of proteins in the cell is being coordinated by heat shock proteins (HSPs). HSP90 plays a major role in it. This can be reflected in cancer therapy. Neverdauskas et al. synthesized benzimidazole derivatives with resorcinol (16) and (17), as potential inhibitors for HSP90 (Figure 5) [39].
Figure 5.
Benzimidazole derivatives (compound 16 and 17) for the inhibition of HSP90.
Benzimidazole is considered a privileged molecule in the medicinal world. Hernández-Romero et al. in 2021 synthesized first-row transition metal compounds which contain benzimidazole moieties (18–21) as ligands in them (Figure 6) [40]. The advancement of metallodrugs for the treatment of cancer has been rapidly evolving. The use of benzimidazole as mono-, di-, tri-, and tetradentate ligands with metals like Cu, Co, Zn, Ni, Mn, V, and Fe led to the formation of effective drugs for cancer therapy by increasing the cytotoxic and antiproliferative activity.
Figure 6.
Benzimidazole derivatives (compound 18, 19, 20 and 21) as metallodrugs.
Bistrović et al. synthesized monocationic benzimidazoles (22) and (23), starting from o-phenylenediamines and benzaldehydes having 1,4-disubstituted-1,2,3-triazole motifs and studied its antiproliferative activities [41]. These compounds showed potent and selective activities that are cytostatic against non-small cell lung cancer (A549) in the low nM range and could be because of apoptosis and primary necrosis (Figure 7). Because of the presence of different amidino groups and aromatic substituents, these compounds showed a difference in their cytostatic activities in Western blot analysis. The enzyme p38 MAPK got inhibited by both the compounds as shown by in silico structural analysis.
Figure 7.
Benzimidazole derivatives (compound 22, 23, 24, 25 and 26) with potential inhibition for lung, colon, and breast cancer.
The 1, 3-disubstituted benzimidazoles (24–26) were synthesized starting from o-diphenylamine and their interactions with cancer cells proteins were examined using molecular docking studies (Figure 7) [42]. The biochemical assay of the synthesized compounds were compared by doing theoretical calculations whereas its biological activity was tested against proteins such as colon cancer antigen (ID 2HQ6) and breast cancer (ID 2AR9) by using molecular docking studies. These benzimidazolyl halides were found to be better against the protein molecules studied and of which (26) was found to be more potent in action among the given three.
Synthesis of imidazo[1,2-a]pyrazine appended benzimidazoles (27) and (28) was done, starting from 1,3-dibromobenzene and evaluated its anticancer activities on the inhibition of growth of NCI-60 human cancer cell lines [43]. The antiproliferative activity of these molecules is attributed to causing damage to the DNA of such cells. The planar geometry of these compounds also enhanced the intercalated binding with cancer cells DNA. The cytotoxicity evaluation of the compounds was also done against the human normal cell line (Hek293) and found to be very low with higher LC50 values (Figure 8).
Figure 8.
Benzimidazole derivatives (compound 27, 28, 29 and 30) with NCI-60 cell line inhibition.
Srour et al. in 2020 reported the formation of a novel class of 2-thiazol linked benzimidazoles (29) and studied its inhibiting action against epidermal growth factor receptor (EGFR) (Figure 8). The in vitro studies of the synthesized compounds using erlotinib as a standard drug revealed its suppression activity against EGFR PK inhibitors, which targets human breast cancer (MCF-7) cells. They have also exhibited a very low suppression percentage among normal cells indicating its diminished side effects when used as an antiproliferative drug [44].
Benzimidazole-tethered pyrazoles (30) have been synthesized in multi-steps by the condensation of phenylhydrazine with acetylphenones followed by cyclization, Vilsmeier-Haack formylation and Knoevenagel reactions (Figure 8) [45]. A study of anti-inflammatory and antioxidant activities of the benzimidazoles showed a marked improvement when compared with diclofenac sodium and ascorbic acid as standards respectively. The anticancer activity was shown against human pancreatic cancer cell line AsPCl (progenitor) and SW1990 (squamous) which was also visible in the better binding with B-cell lymphoma in docking studies.
Mn(I) and benzimidazole co-ligands (31) with potential photo-activated carbon monoxide releasing molecules (CORMs) were synthesized and their biological activities were studied (Figure 9) [46]. The CO releasing properties, as well as luminescence intensities of these complexes, differed with the extend of conjugation and with the degree of unsaturation present in the benzimidazole co-ligands. The bioimaging capabilities of these complexes were proved by the absorption of it by liver cancer cells (SK-Hep1) and human liver cells (HL-7702) under cellular fluorescence imaging tests. Complex (31) showed excellent anticancer activities among all the molecules synthesized.
Figure 9.
Derivatives of benzimidazole (compound 31, 32 and 33) with anticancer activity against liver, lung, and gastric cancer cells.
Prosser et al. synthesized a Cu(II) complex of benzimidazole (32) and studied their anticancer properties [47]. This derivative that was revised at the non-coordinated nitrogen of the benzimidazole molecules, exhibited excellent cytotoxicity against A549 adenocarcinomic alveolar basal epithelial cells (Figure 9).
Research works concentrating on the effective therapeutic agent possessing antiproliferative activity for human gastric cancer paved the way to the discovery of yet another benzimidazole derivative (33) with quinoline copper-based complex (Figure 9) [48]. The complex ensures G2/M phase arrest, apoptosis, mitochondrial dysfunction etc. and thus provides effective cytotoxicity.
Aromatase inhibitors (AIs) are compounds that control estrogen-related diseases and hence breast cancer, as its concentration was found to be higher in such cases. Çevik et al. in 2020 synthesized some novel benzimidazole- triazolothiadiazine libraries and examined its aromatase inhibition activities [49]. Initial screening of these compounds towards anticancer properties against breast cancer cell line (MCF-7) in humans, resulted in getting good results. Upon further subjecting it to in vitro aromatase enzyme inhibition studies, the compound (34).
among them was found to be almost equal in activity when compared with a reference drug letrozole (Figure 10).
Figure 10.
Benzimidazole derivatives (compound 34, 35, 36, 37, 38 and 39) provide inhibition against breast, lung, and prostate cancer cells.
The role of benzimidazole compounds in the treatment of breast cancer is exemplary. Gangrade et al. demonstrated the use of benzimidazole derivatives in the inhibition of Wnt/β-catenin signaling [50]. The upregulation of Wnt/β-catenin signaling in triple-negative breast cancer (TNBC), when compared to normal and other breast cancer subtypes, is inevitable. Benzimidazole compounds like SRI33576 (35) and SRI35889 (36) have a high cytotoxicity rate in TNBC cell lines. They are found to be active inhibitors of Wnt/β-catenin signaling and have therapeutic properties for treating TNBC (Figure 10).
Cheong and co-workers designed and synthesized benzimidazole methylcarbamate analogue (37) with enhanced water solubility [51]. The existed drugs that account for the treatment of metastatic cancers are not suitably aiding the circumstances. Poorly soluble benzimidazole methylcarbamate drugs, which are effective anthelmintics are subjected to functionalization with oxetane or an amine group to improve the solubility and then used as an active therapeutic agent for the treatment of metastatic cancers. Cytotoxicity towards prostate, lung, and ovarian cancers is exhibited by the novel oxetanyl substituted compound (37) (Figure 10).
Liang and co-workers synthesized selenium-containing benzimidazole derivatives through condensation of peptide coupling reagents and irradiation of microwaves [52]. These selenediazole derivatives were recognized as potent anticancer agents against MDA-MB-231 and MCF-7 breast cancer cell lines. Compounds (38) and (39) showed greater cytotoxic activity towards triple-negative breast cancer cell line MDA-MB-231 (Figure 10).
Husain et al. prepared various derivatives of furanone appended benzimidazoles, which effectively contribute to cancer therapy [53]. Compound (40) was found active against DU145 and MCF7 whereas compound (41) has got excellent activity against MCF7, A549, and DU145 cell lines (Figure 11). They are potential cytotoxic agents than the standard drug doxorubicin.
Figure 11.
Benzimidazole analogs (compound 40, 41, 42, 43, 44, 45, 46 and 47) with anticancer activities.
Compounds (42) and (43) are bis-benzimidazole analogs that have been synthesized to account for cancer therapy under microwave irradiation [54]. The anticancer activity was studied with the help of.
Molinspiration software and they possess high bioactivity scores. It was also found that they obey Lipinski’s rule and could be emerged as a lead anticancer drug (Figure 11).
Shinde and co-workers used D-glucose as the precursor for the synthesis of ribofuranosyl nucleosides (44) and (45) (Figure 11). Evaluation of their anticancer activity was done using the MDA-MB-231 cell line [55].
Sireesha et al. designed and synthesized benzimidazole/benzoxazole-linked β-carbolines (46) by the condensation of two various anti-cancer fragments (Figure 11) [56]. With the assistance of MTT assay, these compounds were subjected for the anti-cancer screening against Colo-205 (colon), MCF-7 (breast), A2780 (ovarian), and A549 (lung) and found that these exhibits maximum anti-cancer activity with the β-carbolines hybrid.
Benzimidazole derivatives (47) with a pyrrolidine side chain can be effectively used to treat sorafenib resistance (SR) in hepatocellular carcinoma, was reported in 2019 [57]. Mode of action is through the inhibition of proliferation of SR cell lines by interrupting the phosphorylation of AKT, p70S6, and the downstream molecule RPS6 (Figure 11).
Synthesis of organoruthenium(II) complexes of benzimidazoles (48) and (49) was reported by Welsh and coworkers (Figure 12) [58]. Their anti-cancer activity was screened against triple-negative MDA-MB-231 and MCF-7 breast cancer cell lines, respectively. Among the synthesized compounds, (48) showed more potency and (49) showed comparable potency with the cisplatin, against the MCF-7 cell line.
Figure 12.
Organoruthenium benzimidazole derivatives (compound 48 and 49) with inhibition against breast cancer cell lines.
2.2 Antibacterial and antifungal activity
Heterocyclic appended benzimidazoles were synthesized and their antibacterial and antifungal activities were tested [59]. The mechanism of action of these molecules was also examined by using docking studies with bacterial proteins such as DNA gyrase subunit B (DNAG) and penicillin-binding protein 1a (PBP1a). The compounds with thiazole and thiadiazole moieties (50) and (51) respectively, showed marked inhibitory activity against Escherichia coli, Bacillus pumilus, and Staphylococcus aureus bacteria (Figure 13).
Figure 13.
Benzimidazole derivatives (compound 50, 51, 52 and 53) with inhibitory activity against common bacteria.
Ajani et al. synthesized various o-substituted and 1, 2-disubstituted benzimidazoles and examined their antibacterial properties [60].
Benzene-1,2- diamine undergoes condensation reactions with anthranilic acid, 3, 5-dinitrophenylbenzoic acid, and phenylacetic acid, catalyzed by NH4Cl yielded the precursor molecules, which on reaction with electrophile-releasing agents produced the corresponding o-substituted and 1,2-disubstituted benzimidazoles (52) and (53), respectively (Figure 13). In vitro studies of these compounds showed a better activity with a low minimum inhibitory concentration (MIC) value.
1-aryl-substituted 1, 2, 3-triazole appended amidinobenzimidazoles linked via phenoxymethylene units (54) and (55) were synthesized and their anti-bacterial as well as anti-trypanosomal activities and DNA/RNA binding affinities, were studied [61]. Compound (54) showed a remarked inhibition against gram-positive bacteria whereas compound (55) showed inhibition against gram-negative bacteria. These compounds also showed binding affinities towards ctDNA. Compound (56) with N-isopropylamidine and p-methoxyphenyl-1,2,3-triazole units exhibited enhanced anti-trypanosomal activities against T. brucei and reduced toxicity towards mammalian cells (Figure 14).
Figure 14.
Benzimidazole derivatives (compound 54, 55 and 56) with antibacterial and anti-trypanosomal activities.
A microwave-assisted, Ni(II) catalyzed novel preparation of 2,6-disubstituted and 1,2,6-trisubstituted benzimidazoles were achieved by Patel and his group (Figure 15) [62]. The in-vitro antimicrobial studies of the title compounds (57) against gram-positive and gram-negative bacteria and fungal strains showed an improved activity exhibited by them when compared with ampicillin, a standard drug. Certain compounds show potent anti-mycobacterium tuberculosis activity, antimalarial activity, antioxidant activity, etc. All these activities were supported by better molecular docking scores and their pharmacokinetics were also examined by ADME-Tox descriptors.
Figure 15.
Benzimidazole derivatives (compound 57, 58, 59 and 60) with antibacterial and antimycobacterial activities.
A comparative antimycobacterial activity study of 2,5-disubstituted and 1,2,5-trisubstituted benzimidazoles was reported in 2020 [63]. The in vitro studies against Mycobacterium tuberculosis H37Rv strain revealed an increased activity correlated with lipophilicity for disubstituted compounds (58–60) than for trisubstituted ones because of the addition of a long hydrocarbon chain at position 1 in the latter (Figure 15).
A library of mono and disubstituted benzimidazoles were synthesized by applying different methodologies, i.e., by using the microwave, ultrasound (US), infrared (IR), simultaneous application of US and IR, and by conventional heating [64]. The antimicrobial and antifungal activities of these benzimidazole derivatives were then evaluated. It was found that some compounds such as (61) and (62), were proved to be a better substitute than the standard drugs trimethoprim sulfamethoxazole and miconazole for antimicrobial and antifungal activities, respectively (Figure 16).
Figure 16.
Potential benzimidazole-derived antibiotics (compound 61, 62, 63, 64 and 65).
Very recently, Khan et al. designed and synthesized pyrimidine-benzimidazole hybrids (63) using the revised Biginelli reaction and evaluated its potential inhibition of SARS-CoV-2 main protease and spike glycoprotein [65]. Investigation about the pharmacological properties resulted in biological evidence like antimicrobial and antifungal properties. The derivatives developed possess more affinity in binding and anti-SARS-CoV-2 activity than presently approved drugs (Figure 16).
Zha et al. demonstrated benzimidazole derivatives (64) and (65) as potent antibacterial agents (Figure 16) [66]. Properties like enzyme inhibition, DNA binding, and having a synergistic effect with existing antibiotics makes benzimidazole an active warrior against methicillin-resistance Staphylococcus aureus (MRSA).
Claisen-Schmidt condensation of 2-acetylbenzimidazole and aldehydes followed by a series of steps resulted in the synthesis of benzimidazole derivative (66) [67]. They exhibit exceptional anti-microbial and anti-bacterial activities. The grafting of certain functional groups and the presence of pyridine, pyrimidine, indole, etc. improvises the anti-microbial activity (Figure 17).
Figure 17.
Benzimidazole derivatives (compound 66, 67, 68 and 69) with antimicrobial, antifungal, and antibacterial activities.
Karaburun et al. described the multi-step synthesis of a series of benzimidazole-1,3,4-oxadiazole derivatives (67) which are prominent for their antifungal activities against Candida species [68]. The ergosterol inhibition power was proven via ergosterol quantification assay and the docking studies were performed on 14-α-sterol (Figure 17).
Recently, Aroso and co-workers computationally designed benzimidazole derivatives through palladium-catalyzed reactions [69]. The reaction between 4-bromo-1,2-diaminobenzene and 2-nitrobenzaldehyde, followed by a couple of palladium-catalyzed Suzuki–Miyaura and Buchwald-Hartwig amination cross-coupling reactions resulted in the formation of (68) and (69) (Figure 17). The importance of these benzimidazoles is that it has an inhibitory effect on E. coli DNA gyrase B.
Chen et al. designed flavonoid analogs (70) which consist of benzimidazole derivatives like 4H–chromen-4-one, which provides a remarkable anti-bacterial resistance against members of Xanthomonas and Ralstonia solanacearum (Figure 18) [70]. Molecular docking studies showed the curative and protective activity for the Tobacco mosaic virus (TMV). The inhibition rate value is high for these analogs when compared with other anti-viral agents.
Figure 18.
Derivatives of benzimidazoles (compound 70, 71, 72 and 73) with potential antibacterial, antifungal, and cytotoxic activities.
Compound (71) synthesized by Gençer and co-workers were tested against Candida species through microdilution methods [71]. MTT assay and other various microbiological studies provided the antifungal profile with good and effective in vitro cytotoxic effects along with inhibition on ergosterol biosynthesis (Figure 18).
Synthesis of benzimidazole derivatives like triazinane (72) and oxidiazinanes (73) through the process of amino methylation with the aid of different aryl-N, N′ unsymmetrical thioureas were designed by Gullapelli and co-workers (Figure 18) [72]. The antibacterial activity was evaluated by using suitable gram-positive and negative bacterial strains.
Wang et al. reported the synthesis of a series of benzimidazole moieties (74–76) with quinolone analogs which exhibited antibacterial and antifungal properties (Figure 19) [73]. The bioactive assay proved that the 2-fluorobenzyl derivative has got remarkable antimicrobial activities against the P. aeruginosa and C. tropicalis.
Figure 19.
Quinolone analogs of benzimidazole (compound 74, 75 and 76) with antibacterial and antifungal activities.
A novel, one-pot synthesis of 2-substituted benzimidazoles and Mannich bases (77–80) with potent antimicrobial activity was reported by Marinescu et al. [74].
Qualitative and quantitative antimicrobial bioassay of these benzimidazole derivatives showed activity against a broad spectrum of gram-positive and negative bacterial strains both in planktonic and adherent states. The presence of nucleophilic groups like -OH or -CH3 accounts for the microbicidal activity (Figure 20).
Figure 20.
Potent antimicrobial derivatives of benzimidazole (compound 77, 78, 79 and 80).
Benzimidazoles moieties linked with N-acyl substituted indole (81–86) were demonstrated by Abraham et al. [75]. The assessment of antimicrobial activity was done against gram-negative and gram-positive bacteria like Pseudomonas aeruginosa (MTCC424), Staphylococcus aureus (MTCC 2940), Escherichia coli (MTCC 443), and Enterococcus fecalis. These compounds also account for the hindering of biofilm formation and then the effective growth of Staphylococcus epidermis (Figure 21). Along with this, an HRBC membrane stabilization test was carried out for the evaluation of the anti-inflammatory activity.
Figure 21.
N-acyl substituted indole-linked benzimidazole derivatives (compound 81, 82, 83, 84, 85 and 86) as antimicrobial agents.
Antoci and co-workers synthesized bis-(imidazole/benzimidazole)-pyridine derivatives (87) through N-alkylation (Figure 22) [76]. The anti-TB activity of the compound is good to excellent against both replicating and nonreplicating Mtb. The derivatives are effective against drug-resistant Mtb and some possess a bactericidal approach.
Figure 22.
Benzimidazole derivatives (compound 87, 88, 89 and 90) with antibacterial and anti-TB activities.
The synthesis of naphthyl-substituted benzimidazole derivatives (88) and (89) was reported by Ersan et al. in 2020 [77]. The antimicrobial activity was screened and was found that (89) showed maximum potency against all gram-positive and gram-negative bacteria. Also, (88) actively functions as an antifungal agent. These derivatives also interact with active sites of E. coli and can be accounted for inhibition of E. coli topoisomerase I (Figure 22).
Sirim et al. designed and synthesized benzimidazole-acrylonitrile hybrid derivatives from benzene-1, 2-phenyleneamine and ethyl cyanoacetate followed by reaction with piperazines [78]. All the derived compounds exhibited anti-mycobacterial activity against M. tuberculosis H37Rv strain by microplate alamar blue assay (MABA). Compound (90) was found to be more effective than standard drugs like isoniazid, ciprofloxacin, rifampicin, etc. (Figure 22).
2.3 Antiparasitic activity
Taman et al. evaluated the antischistosomal activity of newly synthesized benzimidazole-related compounds like NBTP-OH (91) and NBTP-F (92) [79]. The Suzuki-Miyaura coupling reaction of 5-formyl thiophen-2-ylboronic acid and 1-bromo-4-hydroxy benzene or 1-bromo-4-flouro benzene followed by a series of reactions resulted in the formation of compounds (91) and (92), respectively (Figure 23). To date, the treatment of schistosomiasis depended on Praziquantel (PZQ). The use of these two structurally related benzimidazole derivatives can be an alternative for PZQ. The in vitro schistosomicidal assay performed on adult worms gave the conclusion that they were considered dead through the destruction of tegument after two minutes of treatment with 91 and 92.
Figure 23.
Benzimidazole derivatives (compound 91, 92, 93 and 94) with antischistosomal and anti-trichinellosis activities.
Synthesis of 1, 3-disubstituted benzimidazol-2-ones (93) and (94) starting from o-phenylenediamine and urea, followed by the evaluation of its anti-trichinellosis efficacy was done [80]. It was found that the synthesized benzimidazole derivatives are more effective than the standard drug albendazole, which is the traditional drug used in the treatment against Trichinella spiralis. The estimation of antiparasitic activity was employed through the Campbell method. Selective binding of benzimidazole moiety with the β-tubulin of the parasite results in the destruction of the cell, followed by the death of the parasite. The in vitro activity of all the tested benzimidazole analogs increases with the concentration against the Trichinella spiralis (Figure 23).
Molecular docking studies and quantitative structure–activity relationship (QSAR) delivered that benzimidazole derivatives (95–97) can be used as cruzain inhibitors for the deadly Chagas disease [81]. The model compounds used displayed a high statistical consistency and a notable capability to predict the inhibiting sites (Figure 24). The scenario with Chagas disease is the unavailability of an effective treatment method. Clinical studies related to the Chagas disease and cruzain inhibitors have been on the account of research scientists. In short, benzimidazole derivatives can be used as a lead in the drug discovery of Chagas disease by acting against the recombinant cruzain enzyme.
Figure 24.
Benzimidazole derivatives (compound 95, 96 and 97) as cruzain inhibitors for Chagas disease.
Tonelli et al. designed and synthesized benzimidazole derivatives from benzene-1, 2-diamine and various acids followed by suitable functionalization and used it as a potent antileishmanial agent [82]. Benzimidazole derivatives were tested against Leishmania tropica and L. infantum and were found that compounds bearing the derivatives of 1-lupinyl were commonly more active than dialkylaminoalkyl derivatives and compounds (98) exhibited the highest potency among the synthesized compounds (Figure 25). The observed antileishmanial activity was a result of the interaction of benzimidazole derivatives with acidic components of the cell membrane leading to its destruction.
Figure 25.
Compounds 98, 99 and 100 with antileishmanial and antiparasitic activities.
Exploration of the inhibitory activity of certain benzimidazole compounds like albendazole (3), ricobendazole (99), oxfendazole (100) etc. resulted in acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibition at nanomolar level [83]. This has got immense importance in therapy emerging for handling the resistance among anti-cholinergic factors and in antiparasitic treatment (Figure 25). The benzimidazole derivatives are selectively toxic towards helminths which are considered parasites. The inhibitive effect of benzimidazole derivatives on β-tubulin leads to disruption of function in helminths and results in its death.
2.4 Antiviral activity
Compound (101) has been synthesized in a multi-step process by Bessieres et al. in 2021 (Figure 26) [84]. A study about the inhibition of Ebola virus infection resulted in the design of a more potent and selective drug than the reference drug, Toremifene.
Figure 26.
Potential antiviral derivatives of benzimidazole (compound 101, 102, 103 and 104).
Ibba et al. demonstrated the role of benzimidazole derivatives (102) and (103), which are active inhibitory agents against enterovirus A71 (EV-A71), which is a major cause for foot-mouth disease (HFMD), herpangina, etc. [85]. Penetration and apoptosis assay concluded that the derivatives are capable to inhibit viral endocytosis through reduced viral attachment and penetration to the host cells (Figure 26).
Research for the inhibitory action of chikungunya virus (CHIKV) infection led to the discovery of benzimidazole-related antiviral agent which targets the nonstructural protein 4 (nsP4), was reported by Wada and co-workers [86]. One of the compounds (104), synthesized by them can effectively inhibit CHIKV by using M2295 residue in the nonstructural protein 4 (nsP4) and with the help of CHIKV replicons, it inhibits the RNA-dependent RNA-polymerase (RdRp) function of CHIKV (Figure 26).
2.5 Other properties like antipsychotic, antidiabetic, anticoagulant activities, etc.
In vitro and in vivo characteristic studies of benzimidazole acetamide derivatives (105) in the ethanol-induced neuro-degeneration model was performed by.
Imran et al. in 2021 [87]. The derivatives lowered the neurodegeneration and inflammation of neurons by down-regulating inflammatory cascades caused by oxidative stress (Figure 27).
Figure 27.
Benzimidazole derivatives (compound 105, 106, 107, 108 and 109) with antipsychotic, antidiabetic, and anticoagulant activities.
The prominence of benzimidazole in the field of medicine is exceptional. Etazene (106), a benzimidazole opioid that has got strong analgesic activity, is used as a new psychoactive substance (Figure 27) [88]. Misuse of certain benzimidazole derivatives can create social crises too.
Tantray and co-workers studied psychiatric disorders like depression and acknowledged the fact that glycogen synthase kinase-3β (GSK-3β) dysfunction is a potential implication [89]. They designed and synthesized several 1,3,4-oxadiazole carboxamides linked to benzimidazoles (107) and assessed their in vitro GSK-3β inhibition. It was found that these molecules are having antidepressant activity (Figure 27).
Hussain et al. synthesized certain benzimidazole analogs (108) for the effective management of type-II diabetics [90]. The sulfonamide bearing 2-marcaptobenzimidazoles (108), possesses better in vitro α-amylase enzyme inhibitory activity while compared with the standard drug, acarbose (Figure 27).
Dabigatran is an effective drug having a benzimidazole core as the activity center and is used for the treatment of cardiovascular diseases because of its antithrombin as well as anticoagulant activities. Zhang et al. in 2020 enhanced the activity and bioavailability of dabigatran by adding methyl and methoxy groups into the benzene ring [91]. By studying the anticoagulant action and thrombin inhibition properties of compounds (109) in rats, proved the possibility of using these molecules as potential antithrombin drug candidates in the future (Figure 27).
3. Conclusions
To sum up, benzimidazole is a chemical compound that belongs to the family of heterocyclic aromatic organic compounds. It is a potent biologically important molecule with a noticeable therapeutic activity. Applications of benzimidazole extend to medicinal chemistry. Several advanced research in this area also found out that the aforementioned compound has significant antimicrobial activities especially against many strains of viruses, fungus, bacteria, etc. It is also widely used in medicinal chemistry as an accepted drug against parasites and their allied infections. Benzimidazole is also used as an analgesic and anti-inflammatory agent. Recent studies have also created a lot of attention for the compound since it has an anti-carcinogenic activity like cytotoxicity and hence may become a viable cure for cancer in the future. The applications of benzimidazole cannot be marginalized. It has got a whole spectrum of medicinal agents. Benzimidazole has gained popularity in material science.
Apart from this, the multi-target capability of benzimidazole scaffolds has not been explored extensively. Being a versatile motif, benzimidazole could provide a plethora of novel multi-target ligands against various debilitated pathological conditions. The lack of comprehensive compilation about the SAR of many compounds and the various research reports stemmed the reason for less number of active benzimidazole compounds reaching the market. The existing design of benzimidazole derivatives can be further revised to accommodate potential multitargeting agents, thus enhancing and treating multifactorial disorders. This can be a breakthrough establishment in benzimidazole history.
In short, the importance of this imidazoline compound has been proved by the number of research papers getting published in a short period. This chapter is trying to narrate the formulation as well as execution of benzimidazoles in different fields of medicinal chemistry.
Acknowledgments
The authors would like to acknowledge the support given by the Department of Chemistry, Amrita Vishwa Vidyapeetham, Amritapuri campus for providing the necessary facilities to carry out research work.
\n',keywords:"anti-cancer agent, Benzimidazole, biological activity, N-heterocycle, medicinal chemistry, pharmacophore",chapterPDFUrl:"https://cdn.intechopen.com/pdfs/80130.pdf",chapterXML:"https://mts.intechopen.com/source/xml/80130.xml",downloadPdfUrl:"/chapter/pdf-download/80130",previewPdfUrl:"/chapter/pdf-preview/80130",totalDownloads:60,totalViews:0,totalCrossrefCites:0,dateSubmitted:"October 16th 2021",dateReviewed:"December 8th 2021",datePrePublished:"January 19th 2022",datePublished:null,dateFinished:"January 19th 2022",readingETA:"0",abstract:"Benzimidazole, one of the finest classes of heterocyclic aromatic compounds have the characteristic structure of benzene fused with a five-membered imidazole ring. Despite being made their first appearance in the late 1870s, they are considered as a ‘privileged molecule’. The applications of this wonder molecule range from medicinal chemistry to material science. Benzimidazole being a potent inhibitor for various enzymes has got therapeutic effects like anticancer, antimicrobial, anthelmintic, antioxidant, anticonvulsant, antifungal, anti-inflammatory, antiviral, antihistaminic, antipsychotic, etc. It has also made its existence in various branches of medical science viz ophthalmology, neurology, cardiology and more. The applications of benzimidazole are not only limited to the biological field but also expanded to the field of material chemistry as well. This chapter summarizes the pharmacological properties of benzimidazole, illustrated on numerous derivatives since 2016.",reviewType:"peer-reviewed",bibtexUrl:"/chapter/bibtex/80130",risUrl:"/chapter/ris/80130",signatures:"Gopakumar Kavya and Akhil Sivan",book:{id:"10840",type:"book",title:"Benzimidazole",subtitle:null,fullTitle:"Benzimidazole",slug:null,publishedDate:null,bookSignature:"Dr. Pravin Kendrekar and Dr. Vinayak Adimule",coverURL:"https://cdn.intechopen.com/books/images_new/10840.jpg",licenceType:"CC BY 3.0",editedByType:null,isbn:"978-1-80355-121-0",printIsbn:"978-1-80355-120-3",pdfIsbn:"978-1-80355-122-7",isAvailableForWebshopOrdering:!0,editors:[{id:"310674",title:"Dr.",name:"Pravin",middleName:null,surname:"Kendrekar",slug:"pravin-kendrekar",fullName:"Pravin Kendrekar"}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"}},authors:null,sections:[{id:"sec_1",title:"1. Introduction",level:"1"},{id:"sec_2",title:"2. Benzimidazole and its pharmacological significance",level:"1"},{id:"sec_2_2",title:"2.1 Anticancer activity",level:"2"},{id:"sec_3_2",title:"2.2 Antibacterial and antifungal activity",level:"2"},{id:"sec_4_2",title:"2.3 Antiparasitic activity",level:"2"},{id:"sec_5_2",title:"2.4 Antiviral activity",level:"2"},{id:"sec_6_2",title:"2.5 Other properties like antipsychotic, antidiabetic, anticoagulant activities, etc.",level:"2"},{id:"sec_8",title:"3. Conclusions",level:"1"},{id:"sec_9",title:"Acknowledgments",level:"1"}],chapterReferences:[{id:"B1",body:'Woolley DW. Some biological effects produced by benzimidazole and their reversal by purines. The Journal of Biological Chemistry. 1944;152:225-232. DOI: 10.1016/S0021-9258(18)72045-0'},{id:"B2",body:'Hoebrecker F. Ueber reductionsprodukte der nitracetamidverbindungen. Chemische Berichte. 1872;5:920-924. DOI: 10.1002/cber.18720050295'},{id:"B3",body:'Brink NG, Folkers K. Vitamin B12. 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Microwave-assisted syntheses of benzimidazole-containing selenadiazole derivatives that induce cell-cycle arrest and apoptosis in human breast cancer cells by activation of the ROS/AKT pathway. ChemMedChem. 2016;11:2339-2346. DOI: 10.1002/cmdc.201600261'},{id:"B53",body:'Husain A, Bhutani M, Parveen S, Khan SA, Ahmad A, Iqbal MA. Synthesis, in vitro cytotoxicity, ADME, and molecular docking studies of benzimidazole-bearing furanone derivatives. Journal of the Chinese Chemical Society. 2021;68:362-373. DOI: 10.1002/jccs.202000130'},{id:"B54",body:'Rashid M. Design, synthesis and ADMET prediction of bis-benzimidazole as anticancer agent. Bioorganic Chemistry. 2020;96:103576. DOI: 10.1016/j.bioorg.2020.103576'},{id:"B55",body:'Shinde VS, Lawande PP, Sontakke VA, Khan A. Synthesis of benzimidazole nucleosides and their anticancer activity. Carbohydrate Research. 2020;498:108178. 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Antimicrobial evaluation and docking study of some new substituted benzimidazole-2yl derivatives. Bioinorganic Chemistry. 2020;101:103972. DOI: 10.1016/j.bioorg.2020.103972'},{id:"B60",body:'Ajani OO, Tolu-Bolaji OO, Olorunshola SJ, Zhao Y, Aderohunmu DV. Structure-based design of functionalized 2-substituted and 1, 2-disubstituted benzimidazole derivatives and their in vitro antibacterial efficacy. Journal of Advanced Research. 2017;8:703-712. DOI: 10.1016/j.jare.2017.09.003'},{id:"B61",body:'Bistrović A, Krstulović L, Stolić I, Drenjančević D, Talapko J, Taylor MC, et al. Synthesis, anti-bacterial and anti-protozoal activities of amidinobenzimidazole derivatives and their interactions with DNA and RNA. Journal of Enzyme Inhibition and Medicinal Chemistry. 2018;33:1323-1334. DOI: 10.1080/14756366.2018.1484733'},{id:"B62",body:'Bhavsar ZA, Acharya PT, Jethava DJ, Patel DB, Vasava MS, Rajani DP, et al. Microwave assisted synthesis, biological activities, and in silico investigation of some benzimidazole derivatives. Journal of Heterocyclic Chemistry. 2020;57:4215-4238. DOI: 10.1002/jhet.4129'},{id:"B63",body:'Jiménez-Juárez R, Cruz-Chávez W, de Jesús-Ramírez N, Castro-Ramírez GI, Uribe-González I, Martínez-Mejía G, et al. Synthesis and antimycobacterial activity of 2,5-disubstituted and 1,2,5-trisubstituted benzimidazoles. Frontiers in Chemistry. 2020;8:1-12. DOI: 10.3389/fchem.2020.00433'},{id:"B64",body:'Penieres-Carrillo JG, Ríos-Guerra H, Pérez-Flores J, Rodríguez-Molina B, Torres-Reyes Á, Barrera-Téllez F, et al. Reevaluating the synthesis of 2,5-disubstituted-1H-benzimidazole derivatives by different green activation techniques and their biological activity as antifungal and antimicrobial inhibitor. Journal of Heterocyclic Chemistry. 2020;57:436-455. DOI: 10.1002/jhet.3801'},{id:"B65",body:'Khan S, Kale M, Siddiqui F, Nema N. Novel pyrimidine-benzimidazole hybrids with antibacterial and antifungal properties and potential inhibition of SARS-CoV-2 main protease and spike glycoprotein. Digital Chinese Medicine. 2021;4:102-119. DOI: 10.1016/j.dcmed.2021.06.004'},{id:"B66",body:'Zha GF, Preetham HD, Rangappa S, Sharath Kumar KS, Girish YR, Rakesh KP, et al. Benzimidazole analogues as efficient arsenals in war against methicillin-resistance staphylococcus aureus (MRSA) and its SAR studies. Bioorganic Chemistry. 2021;115:105175. DOI: 10.1016/j.bioorg.2021.105175'},{id:"B67",body:'Marinescu M. Synthesis of antimicrobial benzimidazole–pyrazole compounds and their biological activities. Antibiotics. 2021;10:1002. DOI: 10.1016/j.molstruc.2016.10.066'},{id:"B68",body:'Karaburun AÇ, Kaya Çavuşoğlu B, Acar Çevik U, Osmaniye D, Sağlık BN, Levent S, et al. Synthesis and antifungal potential of some novel benzimidazole-1,3,4-oxadiazole compounds. Molecules. 2019;24:191. DOI: 10.3390/molecules24010191'},{id:"B69",body:'Aroso RT, Guedes RC, Pereira MM. Synthesis of computationally designed 2, 5(6)-benzimidazole derivatives via Pd-Catalyzed reactions for potential E. coli DNA gyrase B inhibition. Molecules. 2021;26:1326. DOI: 10.3390/molecules26051326'},{id:"B70",body:'Chen M, Su S, Zhou Q, Tang X, Liu T, Peng F, et al. Antibacterial and antiviral activities and action mechanism of flavonoid derivatives with a benzimidazole moiety. Journal of Saudi Chemical Society. 2021;25:101194. DOI: 10.1016/j.jscs.2020.101194'},{id:"B71",body:'Karaca Gençer H, Acar Çevik U, Levent S, Sağlık BN, Korkut B, Özkay Y, et al. New benzimidazole-1, 2, 4-triazole hybrid compounds: Synthesis, anticandidal activity and cytotoxicity evaluation. Molecules. 2017;22:507. DOI: 10.3390/molecules22040507'},{id:"B72",body:'Gullapelli K, Brahmeshwari G, Ravichander M, Kusuma U. Synthesis, antibacterial and molecular docking studies of new benzimidazole derivatives. Egyptan Journal of Basic Applied Sciences. 2017;4:303-309. DOI: 10.1016/j.ejbas.2017.09.002'},{id:"B73",body:'Wang YN, Bheemanaboina RRY, Gao WW, Kang J, Cai GX, Zhou CH. Discovery of benzimidazole–quinolone hybrids as new cleaving agents toward drug-resistant pseudomonas aeruginosa DNA. ChemMedChem. 2018;13:1004-1017. DOI: 10.1002/cmdc.201700739'},{id:"B74",body:'Marinescu M, Tudorache DG, Marton GI, Zalaru CM, Popa M, Chifiriuc MC, et al. Density functional theory molecular modeling, chemical synthesis, and antimicrobial behaviour of selected benzimidazole derivatives. Journal of Molecular Structure. 2017;1130:463-471. DOI: 10.1016/j.molstruc.2016.10.066'},{id:"B75",body:'Abraham R, Prakash P, Mahendran K, Ramanathan M. A novel series of N-acyl substituted indole-linked benzimidazoles and naphthoimidazoles as potential antiinflammatory, antibiofilm and antimicrobial agents. Microbial Pathogenesis. 2018;114:409-413. DOI: 10.1016/j.micpath.2017.12.021'},{id:"B76",body:'Antoci V, Cucu D, Zbancioc G, Moldoveanu C, Mangalagiu V, Amariucai-Mantu D, et al. Bis-(imidazole/benzimidazole)-pyridine derivatives: Synthesis, structure and antimycobacterial activity. Future Medicinal Chemistry. 2020;12:207-222. DOI: 10.4155/fmc-2019-0063'},{id:"B77",body:'Ersan RH, Yuksel A, Ertan-Bolelli T, Dogen A, Burmaoglu S, Algul O. One-pot synthesis of novel benzimidazoles with a naphthalene moiety as antimicrobial agents and molecular docking studies. Journal of the Chinese Chemical Society. 2021;68:374-383. DOI: 10.1002/jccs.202000125'},{id:"B78",body:'Sirim MM, Krishna VS, Sriram D, Tan OU. Novel benzimidazole-acrylonitrile hybrids and their derivatives: Design, synthesis and antimycobacterial activity. European Journal of Medicinal Chemistry. 2020;188:112010. DOI: 10.1016/j.ejmech.2019.112010'},{id:"B79",body:'Taman A, El-Bardicy S, Tadros M, Ayoub M, Mansour B, El-Shehabi F, et al. In vitro efficacy of new synthetic benzimidazole-related compounds against Schistosoma mansoni adult worms. Asian Pacific Journal of Tropical Medicine. 2020;13:566-572. DOI: 10.4103/1995-7645.296725'},{id:"B80",body:'Mavrova A, Anichina K, Izevbekhai O, Vutchev D, Popova-daskalova G, Yancheva D, et al. New 1, 3-disubsituted benzimidazol-2-ones as a promising scaffold for the antitrichinellosis agents development. Journal of Chemical Technology and Metallurgy. 2021;56:3-9'},{id:"B81",body:'Pauli I, Ferreira LG, de Souza ML, Oliva G, Ferreira RS, Dessoy MA, et al. Molecular modeling, and structure-activity relationships for a series of benzimidazole derivatives as cruzain inhibitors. Future Medicinal Chemistry. 2017;9:641-657. DOI: 10.4155/fmc-2016-0236'},{id:"B82",body:'Tonelli M, Gabriele E, Piazza F, Basilico N, Parapini S, Tasso B, et al. Benzimidazole derivatives endowed with potent antileishmanial activity. Journal of Enzyme Inhibition and Medicinal Chemistry. 2018;33:210-226. DOI: 10.1080/14756366.2017.1410480'},{id:"B83",body:'Türkan F. Investigation of the toxicological and inhibitory effects of some benzimidazole agents on acetylcholinesterase and butyrylcholinesterase enzymes. Archives of Physiology and Biochemistry. 2021;127:97-101. DOI: 10.1080/13813455.2019.1618341'},{id:"B84",body:'Bessières M, Plebanek E, Chatterjee P, Shrivastava-Ranjan P, Flint M, Spiropoulou CF, et al. Design, synthesis and biological evaluation of 2-substituted-6-[(4-substituted-1-piperidyl)methyl]-1H-benzimidazoles as inhibitors of ebola virus infection. European Journal of Medicinal Chemistry. 2021;214:113211. DOI: 10.1016/j.ejmech.2021.113211'},{id:"B85",body:'Ibba R, Carta A, Madeddu S, Caria P, Serreli G, Piras S, et al. Inhibition of enterovirus A71 by a novel 2-phenyl-benzimidazole derivative. Viruses. 2021;13:58. DOI: 10.3390/v13010058'},{id:"B86",body:'Wada Y, Orba Y, Sasaki M, Kobayashi S, Carr MJ, Nobori H, et al. Discovery of a novel antiviral agent targeting the nonstructural protein 4 (nsP4) of chikungunya virus. Virology. 2017;505:102-112. DOI: 10.1016/j.virol.2017.02.014'},{id:"B87",body:'Imran M, Shah FA, Nadeem H, Zeb A, Faheem M, Naz S, et al. Synthesis and biological evaluation of benzimidazole derivatives as potential neuroprotective agents in an ethanol-induced rodent model. ACS Chemical Neuroscience. 2021;12:489-505. DOI: 10.1021/acschemneuro.0c00659'},{id:"B88",body:'Siczek M, Zawadzki M, Siczek M, Chłopaś-Konowałek A, Szpot P. Etazene (N, N-diethyl-2-{[(4-ethoxyphenyl)methyl]-1H-benzimidazol-1-yl}-ethan-1-amine (dihydrochloride)): A novel benzimidazole opioid NPS identified in seized material: Crystal structure and spectroscopic characterization. Forensic Toxicology. 2021;39:146-155. DOI: 10.1007/s11419-020-00552-9'},{id:"B89",body:'Tantray MA, Khan I, Hamid H, Alam MS, Dhulap A, Kalam A. Synthesis of benzimidazole-linked-1,3,4-oxadiazole carboxamides as GSK-3β inhibitors with in vivo antidepressant activity. Bioorganic Chemistry. 2018;77:393-401. DOI: 10.1016/j.bioorg.2018.01.040'},{id:"B90",body:'Hussain S, Taha M, Rahim F, Hayat S, Zaman K, Iqbal N, et al. Synthesis of benzimidazole derivatives as potent inhibitors for α-amylase and their molecular docking study in management of type-II diabetes. Journal of Molecular Structure. 2021;1232:130029. DOI: 10.1016/j.molstruc.2021.130029'},{id:"B91",body:'Zhang T, Liu Q, Ren Y. Design, synthesis and biological activity evaluation of novel methyl substituted benzimidazole derivatives. Tetrahedron. 2020;76:131027. DOI: 10.1016/j.tet.2020.131027'}],footnotes:[],contributors:[{corresp:null,contributorFullName:"Gopakumar Kavya",address:null,affiliation:'
Department of Chemistry, Amrita Vishwa Vidyapeetham, Amritapuri, Kollam, Kerala, India
Department of Chemistry, Amrita Vishwa Vidyapeetham, Amritapuri, Kollam, Kerala, India
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Therefore, the detection of viruses and their fragments or specific DNA sequences becomes an important approach in molecular diagnosis. Here, we present electrochemical genosensors devoted for detection of influenza virus H5N1 gene sequence. We focus our attention on ion-channel mechanism, E-DNA sensors, and genosensors based on redox-active layer. The novel dual DNA electrochemical sensor with “signal-off” and “signal-on” architecture for simultaneous detection of two different sequences of DNA derived from avian influenza virus type H5N1 by means of one electrode is presented. Immunosensors are also adequate analytical devices for detection of pathogens since antibodies are natural receptors responsible for binding of antigens. Thus, the binding selectivity and efficiency are naturally high. 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He is currently a full professor in\nthe Department of Automation and Applied Informatics at the\nsame university. Dr. Voloşencu is the author of ten books, seven\nbook chapters, and more than 160 papers published in journals\nand conference proceedings. He has also edited twelve books and\nhas twenty-seven patents to his name. He is a manager of research grants, editor in\nchief and member of international journal editorial boards, a former plenary speaker, a member of scientific committees, and chair at international conferences. His\nresearch is in the fields of control systems, control of electric drives, fuzzy control\nsystems, neural network applications, fault detection and diagnosis, sensor network\napplications, monitoring of distributed parameter systems, and power ultrasound\napplications. 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Presently he is working as a associate professor in the Dept of Prosthodontics, Rural Dental College, Loni and maintains a successful private practice specialising in Implantology at Rahata.\n\nEmail: drdeepak_mvikhe@yahoo.com..................",institutionString:null,institution:{name:"Pravara Institute of Medical Sciences",country:{name:"India"}}},{id:"204110",title:"Dr.",name:"Ahmed A.",middleName:null,surname:"Madfa",slug:"ahmed-a.-madfa",fullName:"Ahmed A. Madfa",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/204110/images/system/204110.jpg",biography:"Dr. Madfa is currently Associate Professor of Endodontics at Thamar University and a visiting lecturer at Sana'a University and University of Sciences and Technology. He has more than 6 years of experience in teaching. 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She is an editor and reviewer in numerous international journals.",institutionString:"MSA University",institution:null},{id:"204606",title:"Dr.",name:"Serdar",middleName:null,surname:"Gözler",slug:"serdar-gozler",fullName:"Serdar Gözler",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/204606/images/system/204606.jpeg",biography:"Dr. Serdar Gözler has completed his undergraduate studies at the Marmara University Faculty of Dentistry in 1978, followed by an assistantship in the Prosthesis Department of Dicle University Faculty of Dentistry. Starting his PhD work on non-resilient overdentures with Assoc. Prof. Hüsnü Yavuzyılmaz, he continued his studies with Prof. Dr. Gürbüz Öztürk of Istanbul University Faculty of Dentistry Department of Prosthodontics, this time on Gnatology. He attended training programs on occlusion, neurology, neurophysiology, EMG, radiology and biostatistics. In 1982, he presented his PhD thesis \\Gerber and Lauritzen Occlusion Analysis Techniques: Diagnosis Values,\\ at Istanbul University School of Dentistry, Department of Prosthodontics. As he was also working with Prof. Senih Çalıkkocaoğlu on The Physiology of Chewing at the same time, Gözler has written a chapter in Çalıkkocaoğlu\\'s book \\Complete Prostheses\\ entitled \\The Place of Neuromuscular Mechanism in Prosthetic Dentistry.\\ The book was published five times since by the Istanbul University Publications. Having presented in various conferences about occlusion analysis until 1998, Dr. Gözler has also decided to use the T-Scan II occlusion analysis method. Having been personally trained by Dr. Robert Kerstein on this method, Dr. Gözler has been lecturing on the T-Scan Occlusion Analysis Method in conferences both in Turkey and abroad. Dr. Gözler has various articles and presentations on Digital Occlusion Analysis methods. He is now Head of the TMD Clinic at Prosthodontic Department of Faculty of Dentistry , Istanbul Aydın University , Turkey.",institutionString:"Istanbul Aydin University",institution:{name:"Istanbul Aydın University",country:{name:"Turkey"}}},{id:"240870",title:"Ph.D.",name:"Alaa Eddin Omar",middleName:null,surname:"Al Ostwani",slug:"alaa-eddin-omar-al-ostwani",fullName:"Alaa Eddin Omar Al Ostwani",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/240870/images/system/240870.jpeg",biography:"Dr. Al Ostwani Alaa Eddin Omar received his Master in dentistry from Damascus University in 2010, and his Ph.D. in Pediatric Dentistry from Damascus University in 2014. Dr. Al Ostwani is an assistant professor and faculty member at IUST University since 2014. \nDuring his academic experience, he has received several awards including the scientific research award from the Union of Arab Universities, the Syrian gold medal and the international gold medal for invention and creativity. Dr. Al Ostwani is a Member of the International Association of Dental Traumatology and the Syrian Society for Research and Preventive Dentistry since 2017. He is also a Member of the Reviewer Board of International Journal of Dental Medicine (IJDM), and the Indian Journal of Conservative and Endodontics since 2016.",institutionString:"International University for Science and Technology.",institution:{name:"Islamic University of Science and Technology",country:{name:"India"}}},{id:"42847",title:"Dr.",name:"Belma",middleName:null,surname:"Işik Aslan",slug:"belma-isik-aslan",fullName:"Belma Işik Aslan",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/42847/images/system/42847.jpg",biography:"Dr. Belma IşIk Aslan was born in 1976 in Ankara-TURKEY. After graduating from TED Ankara College in 1994, she attended to Gazi University, Faculty of Dentistry in Ankara. She completed her PhD in orthodontic education at Gazi University between 1999-2005. Dr. Işık Aslan stayed at the Providence Hospital Craniofacial Institude and Reconstructive Surgery in Michigan, USA for three months as an observer. She worked as a specialist doctor at Gazi University, Dentistry Faculty, Department of Orthodontics between 2005-2014. She was appointed as associate professor in January, 2014 and as professor in 2021. Dr. Işık Aslan still works as an instructor at the same faculty. She has published a total of 35 articles, 10 book chapters, 39 conference proceedings both internationally and nationally. Also she was the academic editor of the international book 'Current Advances in Orthodontics'. She is a member of the Turkish Orthodontic Society and Turkish Cleft Lip and Palate Society. She is married and has 2 children. Her knowledge of English is at an advanced level.",institutionString:"Gazi University Dentistry Faculty Department of Orthodontics",institution:null},{id:"178412",title:"Associate Prof.",name:"Guhan",middleName:null,surname:"Dergin",slug:"guhan-dergin",fullName:"Guhan Dergin",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/178412/images/6954_n.jpg",biography:"Assoc. Prof. Dr. Gühan Dergin was born in 1973 in Izmit. He graduated from Marmara University Faculty of Dentistry in 1999. He completed his specialty of OMFS surgery in Marmara University Faculty of Dentistry and obtained his PhD degree in 2006. In 2005, he was invited as a visiting doctor in the Oral and Maxillofacial Surgery Department of the University of North Carolina, USA, where he went on a scholarship. Dr. Dergin still continues his academic career as an associate professor in Marmara University Faculty of Dentistry. He has many articles in international and national scientific journals and chapters in books.",institutionString:null,institution:{name:"Marmara University",country:{name:"Turkey"}}},{id:"178414",title:"Prof.",name:"Yusuf",middleName:null,surname:"Emes",slug:"yusuf-emes",fullName:"Yusuf Emes",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/178414/images/6953_n.jpg",biography:"Born in Istanbul in 1974, Dr. Emes graduated from Istanbul University Faculty of Dentistry in 1997 and completed his PhD degree in Istanbul University faculty of Dentistry Department of Oral and Maxillofacial Surgery in 2005. He has papers published in international and national scientific journals, including research articles on implantology, oroantral fistulas, odontogenic cysts, and temporomandibular disorders. Dr. Emes is currently working as a full-time academic staff in Istanbul University faculty of Dentistry Department of Oral and Maxillofacial Surgery.",institutionString:null,institution:{name:"Istanbul University",country:{name:"Turkey"}}},{id:"192229",title:"Ph.D.",name:"Ana Luiza",middleName:null,surname:"De Carvalho Felippini",slug:"ana-luiza-de-carvalho-felippini",fullName:"Ana Luiza De Carvalho Felippini",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/192229/images/system/192229.jpg",biography:null,institutionString:"University of São Paulo",institution:{name:"University of Sao Paulo",country:{name:"Brazil"}}},{id:"256851",title:"Prof.",name:"Ayşe",middleName:null,surname:"Gülşen",slug:"ayse-gulsen",fullName:"Ayşe Gülşen",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/256851/images/9696_n.jpg",biography:"Dr. Ayşe Gülşen graduated in 1990 from Faculty of Dentistry, University of Ankara and did a postgraduate program at University of Gazi. \nShe worked as an observer and research assistant in Craniofacial Surgery Departments in New York, Providence Hospital in Michigan and Chang Gung Memorial Hospital in Taiwan. \nShe works as Craniofacial Orthodontist in Department of Aesthetic, Plastic and Reconstructive Surgery, Faculty of Medicine, University of Gazi, Ankara Turkey since 2004.",institutionString:"Univeristy of Gazi",institution:null},{id:"255366",title:"Prof.",name:"Tosun",middleName:null,surname:"Tosun",slug:"tosun-tosun",fullName:"Tosun Tosun",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/255366/images/7347_n.jpg",biography:"Graduated at the Faculty of Dentistry, University of Istanbul, Turkey in 1989;\nVisitor Assistant at the University of Padua, Italy and Branemark Osseointegration Center of Treviso, Italy between 1993-94;\nPhD thesis on oral implantology in University of Istanbul and was awarded the academic title “Dr.med.dent.”, 1997;\nHe was awarded the academic title “Doç.Dr.” (Associated Professor) in 2003;\nProficiency in Botulinum Toxin Applications, Reading-UK in 2009;\nMastership, RWTH Certificate in Laser Therapy in Dentistry, AALZ-Aachen University, Germany 2009-11;\nMaster of Science (MSc) in Laser Dentistry, University of Genoa, Italy 2013-14.\n\nDr.Tosun worked as Research Assistant in the Department of Oral Implantology, Faculty of Dentistry, University of Istanbul between 1990-2002. \nHe worked part-time as Consultant surgeon in Harvard Medical International Hospitals and John Hopkins Medicine, Istanbul between years 2007-09.\u2028He was contract Professor in the Department of Surgical and Diagnostic Sciences (DI.S.C.), Medical School, University of Genova, Italy between years 2011-16. \nSince 2015 he is visiting Professor at Medical School, University of Plovdiv, Bulgaria. \nCurrently he is Associated Prof.Dr. at the Dental School, Oral Surgery Dept., Istanbul Aydin University and since 2003 he works in his own private clinic in Istanbul, Turkey.\u2028\nDr.Tosun is reviewer in journal ‘Laser in Medical Sciences’, reviewer in journal ‘Folia Medica\\', a Fellow of the International Team for Implantology, Clinical Lecturer of DGZI German Association of Oral Implantology, Expert Lecturer of Laser&Health Academy, Country Representative of World Federation for Laser Dentistry, member of European Federation of Periodontology, member of Academy of Laser Dentistry. Dr.Tosun presents papers in international and national congresses and has scientific publications in international and national journals. He speaks english, spanish, italian and french.",institutionString:null,institution:{name:"Istanbul Aydın University",country:{name:"Turkey"}}},{id:"171887",title:"Prof.",name:"Zühre",middleName:null,surname:"Akarslan",slug:"zuhre-akarslan",fullName:"Zühre Akarslan",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/171887/images/system/171887.jpg",biography:"Zühre Akarslan was born in 1977 in Cyprus. She graduated from Gazi University Faculty of Dentistry, Ankara, Turkey in 2000. \r\nLater she received her Ph.D. degree from the Oral Diagnosis and Radiology Department; which was recently renamed as Oral and Dentomaxillofacial Radiology, from the same university. \r\nShe is working as a full-time Associate Professor and is a lecturer and an academic researcher. \r\nHer expertise areas are dental caries, cancer, dental fear and anxiety, gag reflex in dentistry, oral medicine, and dentomaxillofacial radiology.",institutionString:"Gazi University",institution:{name:"Gazi University",country:{name:"Turkey"}}},{id:"256417",title:"Associate Prof.",name:"Sanaz",middleName:null,surname:"Sadry",slug:"sanaz-sadry",fullName:"Sanaz Sadry",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/256417/images/8106_n.jpg",biography:null,institutionString:null,institution:null},{id:"272237",title:"Dr.",name:"Pinar",middleName:"Kiymet",surname:"Karataban",slug:"pinar-karataban",fullName:"Pinar Karataban",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/272237/images/8911_n.png",biography:"Assist.Prof.Dr.Pınar Kıymet Karataban, DDS PhD \n\nDr.Pınar Kıymet Karataban was born in Istanbul in 1975. After her graduation from Marmara University Faculty of Dentistry in 1998 she started her PhD in Paediatric Dentistry focused on children with special needs; mainly children with Cerebral Palsy. She finished her pHD thesis entitled \\'Investigation of occlusion via cast analysis and evaluation of dental caries prevalance, periodontal status and muscle dysfunctions in children with cerebral palsy” in 2008. She got her Assist. Proffessor degree in Istanbul Aydın University Paediatric Dentistry Department in 2015-2018. ın 2019 she started her new career in Bahcesehir University, Istanbul as Head of Department of Pediatric Dentistry. In 2020 she was accepted to BAU International University, Batumi as Professor of Pediatric Dentistry. She’s a lecturer in the same university meanwhile working part-time in private practice in Ege Dental Studio (https://www.egedisklinigi.com/) a multidisciplinary dental clinic in Istanbul. Her main interests are paleodontology, ancient and contemporary dentistry, oral microbiology, cerebral palsy and special care dentistry. She has national and international publications, scientific reports and is a member of IAPO (International Association for Paleodontology), IADH (International Association of Disability and Oral Health) and EAPD (European Association of Pediatric Dentistry).",institutionString:null,institution:null},{id:"202198",title:"Dr.",name:"Buket",middleName:null,surname:"Aybar",slug:"buket-aybar",fullName:"Buket Aybar",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/202198/images/6955_n.jpg",biography:"Buket Aybar, DDS, PhD, was born in 1971. She graduated from Istanbul University, Faculty of Dentistry, in 1992 and completed her PhD degree on Oral and Maxillofacial Surgery in Istanbul University in 1997.\nDr. Aybar is currently a full-time professor in Istanbul University, Faculty of Dentistry Department of Oral and Maxillofacial Surgery. She has teaching responsibilities in graduate and postgraduate programs. Her clinical practice includes mainly dentoalveolar surgery.\nHer topics of interest are biomaterials science and cell culture studies. She has many articles in international and national scientific journals and chapters in books; she also has participated in several scientific projects supported by Istanbul University Research fund.",institutionString:null,institution:null},{id:"260116",title:"Dr.",name:"Mehmet",middleName:null,surname:"Yaltirik",slug:"mehmet-yaltirik",fullName:"Mehmet Yaltirik",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/260116/images/7413_n.jpg",biography:"Birth Date 25.09.1965\r\nBirth Place Adana- Turkey\r\nSex Male\r\nMarrial Status Bachelor\r\nDriving License Acquired\r\nMother Tongue Turkish\r\n\r\nAddress:\r\nWork:University of Istanbul,Faculty of Dentistry, Department of Oral Surgery and Oral Medicine 34093 Capa,Istanbul- TURKIYE",institutionString:null,institution:null},{id:"172009",title:"Dr.",name:"Fatma Deniz",middleName:null,surname:"Uzuner",slug:"fatma-deniz-uzuner",fullName:"Fatma Deniz Uzuner",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/172009/images/7122_n.jpg",biography:"Dr. Deniz Uzuner was born in 1969 in Kocaeli-TURKEY. After graduating from TED Ankara College in 1986, she attended the Hacettepe University, Faculty of Dentistry in Ankara. \nIn 1993 she attended the Gazi University, Faculty of Dentistry, Department of Orthodontics for her PhD education. After finishing the PhD education, she worked as orthodontist in Ankara Dental Hospital under the Turkish Government, Ministry of Health and in a special Orthodontic Clinic till 2011. Between 2011 and 2016, Dr. Deniz Uzuner worked as a specialist in the Department of Orthodontics, Faculty of Dentistry, Gazi University in Ankara/Turkey. In 2016, she was appointed associate professor. Dr. Deniz Uzuner has authored 23 Journal Papers, 3 Book Chapters and has had 39 oral/poster presentations. She is a member of the Turkish Orthodontic Society. Her knowledge of English is at an advanced level.",institutionString:null,institution:null},{id:"332914",title:"Dr.",name:"Muhammad Saad",middleName:null,surname:"Shaikh",slug:"muhammad-saad-shaikh",fullName:"Muhammad Saad Shaikh",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Jinnah Sindh Medical University",country:{name:"Pakistan"}}},{id:"315775",title:"Dr.",name:"Feng",middleName:null,surname:"Luo",slug:"feng-luo",fullName:"Feng Luo",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Sichuan University",country:{name:"China"}}},{id:"423519",title:"Dr.",name:"Sizakele",middleName:null,surname:"Ngwenya",slug:"sizakele-ngwenya",fullName:"Sizakele Ngwenya",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of the Witwatersrand",country:{name:"South Africa"}}},{id:"419270",title:"Dr.",name:"Ann",middleName:null,surname:"Chianchitlert",slug:"ann-chianchitlert",fullName:"Ann Chianchitlert",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Walailak University",country:{name:"Thailand"}}},{id:"419271",title:"Dr.",name:"Diane",middleName:null,surname:"Selvido",slug:"diane-selvido",fullName:"Diane Selvido",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Walailak University",country:{name:"Thailand"}}},{id:"419272",title:"Dr.",name:"Irin",middleName:null,surname:"Sirisoontorn",slug:"irin-sirisoontorn",fullName:"Irin Sirisoontorn",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Walailak University",country:{name:"Thailand"}}},{id:"355660",title:"Dr.",name:"Anitha",middleName:null,surname:"Mani",slug:"anitha-mani",fullName:"Anitha Mani",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"SRM Dental College",country:{name:"India"}}},{id:"355612",title:"Dr.",name:"Janani",middleName:null,surname:"Karthikeyan",slug:"janani-karthikeyan",fullName:"Janani Karthikeyan",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"SRM Dental College",country:{name:"India"}}},{id:"334400",title:"Dr.",name:"Suvetha",middleName:null,surname:"Siva",slug:"suvetha-siva",fullName:"Suvetha Siva",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"SRM Dental College",country:{name:"India"}}}]}},subseries:{item:{id:"93",type:"subseries",title:"Inclusivity and Social Equity",keywords:"Social contract, SDG, Human rights, Inclusiveness, Equity, Democracy, Personal learning, Collaboration, Glocalization",scope:"
\r\n\tThis topic is dedicated to the efforts and promotion of UNESCO SDG4, the UNESCO initiative on the future of education, and the need for a new social contract for education. It aims to disseminate knowledge on policies, strategies, methods, and technologies that increase the resilience and sustainability of the development of the future of education and the new social contract for education. It will also consider the global challenges such as globalization, demographic change, digital transformation, climate change, environment and the social pillars of sustainable development.
\r\n
\r\n\tResponses to the pandemic and the widespread discontent that preceded it must be based on a new social contract and a New Global Deal for education that ensures equal opportunities for all and respects all people’s rights and freedoms (UNESCO; 2021). Such a new social contract, as proposed by UNESCO, must be based on the general principles underlying human rights - inclusion and equality, cooperation and solidarity, and collective responsibility and interconnectedness - and be guided by the following fundamental principle: Ensure that everyone has access to quality education throughout their lives.
\r\n
\r\n\tWe face the dual challenge of delivering on the unfulfilled promise of ensuring the right to quality education for every child, youth, and adult, as well as fully realizing the transformative potential of education as a pathway to a more sustainable collective future. To achieve this, we need a new social contract for education that eliminates inequities while transforming the future. This new social contract must be based on human rights and the principles of non-discrimination, social justice, respect for life, human dignity, and cultural diversity. It must include an ethic of care, reciprocity and solidarity. The new social contract builds on inclusiveness, equity, lifelong learning, SDG, collaboration and personal learning in a global context for democracy.
\r\n
\r\n\tAt an international level, the adoption of the Open Educational Resources recommendation and the Open Science recommendation represents an important step towards building more open and inclusive knowledge societies as well as the achievement of the UN 2030 Agenda. Indeed, implementing the recommendations will help to achieve at least five more Sustainable Development Goals (SDGs) that are intertwined with the topic of this book series, namely SDG 5 (Gender equality), SDG 9 (Industry, innovation and infrastructure), SDG 10 (Reduced inequalities within and across countries), SDG 16 (Peace, justice and strong institutions) and SDG 17 (Partnerships for the goals).
",coverUrl:"https://cdn.intechopen.com/series_topics/covers/93.jpg",hasOnlineFirst:!1,hasPublishedBooks:!1,annualVolume:11977,editor:{id:"210060",title:"Prof. Dr.",name:"Ebba",middleName:null,surname:"Ossiannilsson",slug:"ebba-ossiannilsson",fullName:"Ebba Ossiannilsson",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002g6LkBQAU/Profile_Picture_2022-02-28T13:31:48.png",biography:"Professor Dr. Ebba Ossiannilsson is an independent researcher, expert, consultant, quality auditor and influencer in the fields of open, flexible online and distance learning (OFDL) and the 'new normal'. Her focus is on quality, innovation, leadership, and personalised learning. She works primarily at the strategic and policy levels, both nationally and internationally, and with key international organisations. She is committed to promoting and improving OFDL in the context of SDG4 and the future of education. Ossiannilsson has more than 20 years of experience in her current field, but more than 40 years in the education sector. She works as a reviewer and expert for the European Commission and collaborates with the Joint Research Centre for Quality in Open Education. Ossiannilsson also collaborates with ITCILO and ICoBC (International Council on Badges and Credentials). She is a member of the ICDE Board of Directors and has previously served on the boards of EDEN and EUCEN. Ossiannilsson is a quality expert and reviewer for ICDE, EDEN and the EADTU. She chairs the ICDE OER Advocacy Committee and is a member of the ICDE Quality Network. She is regularly invited as a keynote speaker at conferences. She is a guest editor for several special issues and a member of the editorial board of several scientific journals. She has published more than 200 articles and is currently working on book projects in the field of OFDL. Ossiannilsson is a visiting professor at several international universities and was recently appointed Professor and Research Fellow at Victoria University of Wellington, NZ. Ossiannilsson has been awarded the following fellowships: EDEN Fellows, EDEN Council of Fellows, and Open Education Europe. She is a ICDE OER Ambassador, Open Education Europe Ambassador, GIZ Ambassador for Quality in Digital Learning, and part of the Globe-Community of Digital Learning and Champion of SPARC Europe. On a national level, she is a quality developer at the Swedish Institute for Standards (SIS) and for ISO. She is a member of the Digital Skills and Jobs Coalition Sweden and Vice President of the Swedish Association for Distance Education. She is currently working on a government initiative on quality in distance education at the National Council for Higher Education. 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