Abstract
Various organic chelating agents have many applications in treating the several diseases and they act as antibacterial, antiviral, antimalarial and cytotoxic agents. Among the organic chelating agents thiosemicarbazones and their derivatives play a unique role in various fields of medicine. Thiosemicarbazones and their derivatives find a numerous applications and among them cytotoxic activity occupies a major portion due to the severity of the cancer treatment. In this present chapter we described and discussed the cytotoxic activity of thiosemicarbazones, their derivatives and various metal complexes of them. For this purpose, we reviewed the research articles published in various reputed international journals since 35 years. We summarized the results of those research findings and it is found that among the various metal ions, mostly the platinum and palladium complexes are effective cytotoxic agents than other metal complexes.
Keywords
- thiosemicarbazones
- metal complexes
- cytotoxic activity
- Schiff bases
1. Introduction
A Schiff base is a nitrogen analog of a carbonyl compound (aldehyde or ketone) in which the C=O group is replaced by C=N–R group. Generally, Schiff bases are considered as imines bearing a hydrocarbyl group on the nitrogen atom R2C=NR′ (R′ ≠ H). Schiff bases are usually synthesized by the condensation of a carbonyl compound with a primary amine as shown in the following Figure 1.
Schiff bases had various applications in different fields, such as medical [1], pharmaceutical [2] and biological [3]. Due to the presence of electron donating groups, such as sulfur and nitrogen atoms they can bind with metal ions in enzymes. Among various Schiff bases, thiosemicarbazones occupy a major role by having electron donating nitrogen and sulfur atoms. Thiosemicarbazones are a group of compounds obtained by condensing thiosemicarbazide with carbonyl compounds in the presence of a few drops of glacial acetic acid. These reagents function as good chelating agents and form complexes with several metal ions, by bonding through thionate sulfur atom and hydrazino nitrogen atom. In the last few years, much interest has been directed towards the use of chelating ligands containing sulfur and nitrogen in analytical studies as well as in structural studies of metal complexes. The wide applications and rapid growth in the popularity of sulfur ligands is due to their remarkable property as potential donors to form stable as well as characterized complexes in which the back bonding from the metal ion is possible under favorable conditions. In addition, the presence of nitrogen along with sulfur tends to lower the solubility of the complexes, making the isolation of these complexes easier.
Thiosemicarbazones are having great biological activities due to their ability to coordinate to the metal centers in enzymes. A number of studies reveals the biological and pharmacological activities of thiosemicarbazones and their metal complexes, such as anti-bacterial, anti-viral, anti-malarial and antineoplastic [4]. Anticancer activities of thiosemicarbazones were reported by various authors over worldwide [5]. Because of having various applications, in recent years a large number of authors reported the synthesis and characterization studies of different thiosemicarbazone ligands. The importance of thiosemicarbazones both in analytical and biological fields owe to us to synthesize new thiosemicarbazones.
Based on the starting compounds thiosemicarbazones can be classified into four types as shown below:
Aldehydes or substituted aldehydes with thiosemicarbazide.
Aldehydes or substituted aldehydes with substituted thiosemicarbazide.
Ketones or substituted ketones with thiosemicarbazide, and
Ketones or substituted ketones with substituted thiosemicarbazide.
Depending on the type of parent aldehyde or ketone used for condensation they can act as unidentate, bidentate or multidentate chelating agents during complexation with metal ions. Thio- and/or phenylthiosemicarbazones are synthesized by the condensation of carbonyl compound (with or without substitutes) with thio (phenylthio-) semicarbazides.
2. Cytotoxic activity of metal thiosemicarbazone complexes
2.1 Pd (II) and Pt(II) complexes
Recently many authors were reported the anticancer activity of thiosemicarbazones and their palladium and platinum complexes. Nguyena et al. [6] reported the anticancer activities of Pd(II) and Pt(II) complexes of 1-picolinoyl-4-substituted Thiosemicarbazones against MCF7 and HepG2 cancer cell lines. Anti-proliferative activity of N-Substituted Indole thiosemicarbazones and its Pd(II) complexes against HeLa S3 cancer cell lines was reported by [7]. Nyawade et al. [8] reported cytotoxic activity of 2-acetyl-5-methyl thiophene and cinnamaldehyde thiosemicarbazones and their palladium(II) complexes cytotoxic activity on human cancer cell lines, Caco-2(Colon), HeLa(Cervical), Hept-G2 (hepatocellular) and PC-3 (Prostate) cell lines. Complexes shows excellent activity than ligands. Matesanz et al. [9] studied anticancer activity of Pd(II) and Pt(II) complexes of pyrrol-2-carbaldehyde N-p-chlorophenylthiosemicarbazone.
The palladium complexes of N-Substituted isatin thiosemicarbazones shows significant
Isatin thiosemicarbazone derivatives and its complexes of Pt(II) shows potent activity against human colorectal carcinoma cell line (HCT 116) [13]. 2,6-Diacetylpyridine bis(4N-tolylthiosemicarbazone) complexes of Pd(II) and Pt(II) show the activity against cisplatin resistant A2780cisR tumor cells. These were shows high antiproliferative activity against breast cancer cell MCR-F-7 cells [14]. 2-Oxo-1,2-dihydroquinoline-3-carbaldehyde thiosemicarbazones complexes of Pd(II) shows a good cytotoxic activity against human cancer cell lines such as HeLa, KEp-2, Hep G2, and A431. It was evaluated and found the relationship between the structure and the activity of palladium complexes [15].
6-Methoxy-2-oxo-1,2-dihydro quinoline-3-carbaldehyde 4N-substituted thiosemicarbazones and its complexes of Pd(II) shows better cytotoxic activity against human lung cancer cell line A549 than other complexes and even cisplatin. All the complexes had strong anti-oxidant property [16]. Pd(II), Ni(II), Pt(II) complexes of 5-Acetylbarbituric-4N-dimethylthiosemicarbazones studies show that one of the complex had sufficient cytotoxicity against HeLa cells [17]. 3,5-Diacetyl-1,2,4-triazol bis(4N-substituted thiosemicarbazone) and its complexes of Pd(II) were tested for antiproliferative activity against NCI-H460, A2780 and A2780cisR human cancer cell lines and found that they exhibit low toxicity on kidney cells with respect to cisplatin [18].
Pt(II) complexes of Bis(thiosemicarbazones) of the 3,5-diacetyl-1,2,4-triazol series were tested cytotoxic activity against NCI-H460, A2780, and A2780cisR cancer cell lines and the results indicates that they were active against those cell lines and had high activity against NCI-H460 cell line [19]. 5-Substitutedthiophene-2-Carboxaldehyde thiosemicarbazones and its complexes of Pt(II), Pd(II) shows better cytotoxic activity than free ligand, but palladium complexes shows lesser activity than free ligands [20]. Pt(II) complexes of 3,5-Diacetyl-1,2,4-triazol bis(4,4-dimethylthiosemicarbazone) Anti-proliferative activity of ligand and its complexes was tested against NCI-H460, A2780 and A2780cisR human cancer cell lines. The results show that the compounds exhibits better activity against A2780cisR cell line than cisplatin [21].
2-Acetylpyridine-
2-Acetyl Pyridine N(4)-Ethyl-thiosemicarbazones, 2-Acetyl Pyridine N(4)-1-(2-pyridyl)-piperazinyl TSC, 2-Formyl Pyridine N(4)-1-(2-pyridyl)-piperazinyl TSC and its complexes of Pt(II), Pd(II) shows antiproliferative activity against gram +ve bacteria but not on gram –ve bacteria. Some of the complexes overcome the cisplatin resistance of A2780/Cp8 cells [25]. 2-Acetylpridine thiosemicarbazone and Platinum complexes were effective on gram + bacteria. They were also effective on yeast. Few of the complexes were exhibits antitumor activity [26]. 2-Acetylpyridine and pyridine-2-carbaldehyde N(4)-ethyl thiosemicarbazones and Platinum complexes were found to be overcome the cisplatin resistant tumor cells, A2780/Cp8 [27].
Pyridine-2-carbaldehyde thiosemicarbazone and its complexes of Pd(II) and Pt(II) exhibits the higher in vivo antitumor activity [28]. Pd(II) and its complexes of 3,5-Diacyl-1,2,4-triazole bis(thiosemicarbazone); 2,6-diacylpyridine bis(TSC); benzyl bis(TSC) shows better antitumor activity against several human, monkey and murine cell lines [29].
Isopropylbenzaldehyde thiosemicarbazone and its complexes of Pd(II) and Pt(II) show anticancer activity against several human and murine cell lines were reported by [31]. Phenylacetaldehyde thiosemicarbazone and its complexes of Pd(II) and Pt(II) cytotoxic activity was studied and observed that Cis-DDP-resistant tumor cells has high activity [32].
3,5-Diacyl-1,2,4-triazole bis(thiosemicarbazone); 2,6-diacylpyridine bis(TSC); benzyl bis(TSC) and its Pd(II) complexes shows better antitumor activity against several human, monkey and murine cell lines [29].
Cytotoxic activity of phenylacetaldehyde thiosemicarbazone and its Pd(II) and Pt(II) complexes were studied and it was reported that cis-DDP-resistant tumor cells has reacted highly [32]. 2-Acetylpyridine N(4)-methyl, N(4)-ethyl and N(4)-phenyl thiosemicarbazones and its complexes of Pd(II) Antitumor studies indicates that all the palladium complexes were active in the inhibition of DNA synthesis on P388 and L1210 cell cultures (mice bearing tumors) [33]. 2-Acetylpyridine N(4)-propyl, N(4)-dipropyl- and 3-hexamethyleneiminyl thiosemicarbazones and its Palladium complexes does not had antifungal activity against the tested species. But they had significant anti-tumor activity against P388 and L1212 cell cultures [34].
2.2 Copper complexes
Thiosemicarbazone and its copper (II) complexes exhibits high anticancer activity due its highest stability and membrane permeability [35]. 2-Picoline and 5,5-dimethylbipyridine and its Cu(II) complexes cytotoxic activity was reported on MDA-MB-231 breast cancer cell line [36]. Chitosan-functionalized pyridine-based Thiosemicarbazones and their Cu(II) complexes shows antiproliferative activity against MCDK and MCF-7 cancer cell lines and their complexes shows high cytotoxic activity than ligands [37].
6-Methyl-2-oxo-quinoline-3-carbaldehydethiosemicarbazone and its Cu(II) complexes Cytotoxic activities were evaluated for both the ligand and three complexes. In vitro anti-tumor studies revealed that copper complex shows better activity towards SK-OV-3 and MGC80-3 tumor cell lines than the commercial anticancer drug, cisplatin. But all the complexes show lower activity against human liver cell lines than cisplatin [42]. 3-Phenyl (substituted)-1-pyridin-2-ylprop-2-en-1-one thiosemicarbazone and its Cu(II) Cytotoxic activity were tested against human cancer cell lines such as HL60, MDA-MB 231, and HCT-116. The results indicate that coordination of copper increases the cytotoxic activity of the compounds [43].
Glyoxal-bis(4-methyl-4-phenyl-3-thiosemicarbazone) and its Copper complex has better cytotoxic activity against various human cancer cell lines than the Adriamycin, a commercial drug. The copper complex significantly inhibits the growth of tumor HCT 116 xenografts in nude mice [44]. Cu(II) and its complexes of 2-Oxo-1,2-dihydroquinoline-3-carbaldehyde4(
α-Heterocyclic-N4-substituted thiosemicarbazones and its Cu(II) complex Anti-proliferative activity were tested against breast cancer cell line SK-BR-3. The ligands shows better catalytic inhibition property of topoisomerase-Iiα than complexes [47]. Cu(II) complexes of 2-Acetylpyridine-4,4-dimethyl-3-thiosemicarbazone, di-2-pyridyl ketone-4,4-dimethyl-3-TSC shows better anti-proliferative activity than ligand [48]. 2-Hydroxy-8-R-tricyclo [7.3.1.0.2,7] tridecane-13-one thiosemicarbazone and its complexes of Cu(II), Pd(II) shows Anti-microbial activities and cytotoxic activities of the compounds were reported [49]. Salicylaldehyde semi−/thiosemicarbazones and its complexes of Cu(II) were tested for cytotoxic activity against MCF-7 human breast cancer cell lines. The results revealed that ligands were inactive but copper complex of thiosemicarbazone was more active than others [50].
5-Formyluracil thiosemicarbazone derivatives and its Cu(II) Complexes were exhibits DNA interaction by electrostatic and groove binding. But these were no activity against human leukemic cell line U937 [51]. α-Ketoglutaric acid thiosemicarbazone and its Cu(II) Copper complexes has antiproliferative activity against human cell line U937 and no effect on the K562 cell line [52]. 10-Deacetylbaccatin thiosemicarbazone and its Cu(II) Cytotoxic activity of the ligand and its complex was tested against human breast cancer cell line MCF-7 [53].
Ref. [54] reported the cytotoxic activity of Cu(II) and its complexes of 2-Acetylpyrazone-N-substituted thiosemicarbazones. Ref. [55] studied the anticancer activity of 5-Formyluracil thiosemicarbazone and its Cu(II) complexes against human leukemic cell lines K562 and CEM (Figure 3).
2.3 Cu(II) and Zn(II) complexes
Hydroxyquinoline-thiosemicarbazones and its Cu(II) and Zn(II) complexes shows more cytotoxic activity towards human lung cell lines (A549) than their parent ligands [56]. Methyl pyruvate thiosemicarbazones and its Cu(II), Zn(II) complexes anti-proliferative activity studies reveals that copper complex was most effective on human leukemic cell line U937 than other compounds [57].
2.4 Cu(II) and Ni(II) complexes
Cu(II), Ni(II) complexes and its N-Ethyl-2-(phenyl(pyridin-2-yl)methylene) hydrazine carbothioamide cytotoxic activity was evaluated against human lung cancer cell lines (A549) and normal cell lines (L929). The results indicates that the copper complexes shows better activity than nickel complexes and both complexes were less harmful to normal cells [58]. 2,4′-Dibromoacetophenone thiosemicarbazone and its Cu(II), Ni(II), Pd(II) complexes, Antioxidant and antitumor activities were studied. Nickel complex shows good antitumor activity against HepG2 hepatoblastoma cell lines [59]. Cu(II) and Ni(II) complexes and its Cinnamaldehyde and cuminaldehyde thiosemicarbazones were tested in vitro anti-leukemic activity on U937 human cell line. Metal complexes shows better activity than ligands [60]. 3,4-Difluoroacetophenone thiosemicarbazone; 2-bromo-4′-chloroacetophenone TSC and its Cu(II), Ni(II) complexes were tested for antitumor activity against HepG2 human hepatoblastoma cells. The results indicates that the copper complexes of the both ligands had better activity than others against cancer cell line [61]. (Z)-2-(Amino(pyridin-2-yl) methylene)-N-methylhydrazine carbothioamide and its Cu(II), Zn(II) complexes Cytotoxic activity was studied against HeLa, HepG-2 and SGC-7901 cell lines. The results shows that copper complex had better activity among the others [62].
Bis(citronella thiosemicarbazone); Pyridoxal TSC and its Ni(II), Cu(II) Metal complexes were tested for antiretro-viral activity against HIV-1 and HTLV-1/−2. The results indicates that copper complex has potent anti HIV activity (Figure 4) [63].
2.5 Cu(II), Ni(II) and Zn(II) complexes
2-Methoxybenzaldehyde-S-2-methylbenzyl dithiocarbamate and 3-methoxybenzalde hyde-S-2-methylbenzyl dithiocarbamate and its Cu(II), Ni(II), Zn(II) complexes were inactive against MCF-7 and MDA-MB-231 breast cancer cell lines [64].
2.6 Ni(II) complexes
Ni(II) and its complexes of 3-Methoxy-salicylaldehyde-4(N)-substituted thiosemicarbazones exhibits strong anti-oxidant property with strong radical scavenging ability. Some of the complexes shows better anticancer activity against lung cancer cell lines (A549) than the ligand and cisplatin [11]. N(4)-substituted thiosemicarbazone and its Ni(II) complexes Anti-cancer activity was tested against human breast cancer cell lines (MCF-7). All the complexes shows moderate activity compared to commercial anti-cancer drug, cisplatin [65].
Ni(II) and its complexes of dinucleating bis(thiosemicarbazones) were tested for cytotoxic activity against human cancer cell lines (A549 and HepG2). One of the nickel complex shows better activity against A549 cell line than cisplatin drug [66].
2-Hydroxy-1-naphthaldehydethiosemicarbazone; salicylaldehyde-4(N)-ethylthiosemicarbazone; 2-hydroxy-1-naphtha ldehyde-4(N)-ethyl TSC and Ni(II) complexes were tested for cytotoxic activity against human cancer cell lines (A549 and HepG2). One of the nickel complex shows better activity against A549 cell line than cisplatin drug [67]. Ortho-Naphthaquinone thiosemicarbazone; ortho-Naphthaquinone semicarbazone Anti-cancer activity and its Ni(II) complexes were tested against MCF-7 human breast cancer cell lines and results revealed that semicarbazone and nickel complexes were more active than thiosemicarbazone ligand [68].
2.7 Fe(II) and Fe(III) complexes
α-N-heterocyclic thiosemicarbazone and its complex of Fe(III) Anti-cancer activity was studied against human breast cancer cell lines, cervical cancer cell lines and liver cell lines. The results show that iron complex has better activity than its ligand. This study also evaluates the anti-cancer mechanism [70]. 2-Acetylpyridine thiosemicarbazones and its Fe(III) complexes Antiproliferative property were reported. The structure and activity relationship was determined [71]. 2-Acetylpyridine
Iron and its complexes of Series of Di-2-pyridyl ketone thiosemicarbazones had good antiproliferative activity against the tested tumor cells [73]. 1-Formylisoquinoline thiosemicarbazone; 4-Methyl-5-amino-1-formylisoquinoline TSC and its Fe(II), Fe(III) complexes were active against P 388 lymphocytic leukemia test system in mice (Figure 6) [74].
2.8 Organo Sn complexes
Cytotoxic activity of 2-Hydroxy-5-methoxy benzaldehyde-N(4)-methylthiosemicarbazone and its complexes Organotin (IV) were tested against human colorectal (HCT 116) cell lines and the results show that the complexes had better activity than the ligand [75]. 2-Benzoylpyridine N(4)-phenyl thiosemicarbazone; 2-Acetyl pyrazine N(4)-phenyl TSC and its Diorgano Sn(IV), Antibacterial activity and cytotoxic activity against K562 leukemia cells of the free ligands and complexes were reported [76]. Pyridoxal thiosemicarbazone and its complexes of Diorgano Sn(IV) antitumor activity were studied and observed that Ethyl, butyl, and phenyl substituted compounds suppress the proliferation of friend erythroleukemia cells (Figure 7) [77].
3. Miscellaneous
2-Benzoylpyridine N(4)-cyclohexyl thiosemicarbazone-Anti-proliferative activity of the ligand and its indium complexes was tested against human hepatocellular carcinoma. The studies revealed that the indium complex has better activity than the others [78]. N4-(2-Hydroxy-5-chlorobenzyliden e)-2-amino-5-chlorobenzophenone thiosemicarbazone; N4-(2-Hydroxy naphthalene-1-carbaldehyde)-2-amino-5-chlorobenzophenone TSC and its complexes of Ru(II) cytotoxic activity was studied and reported that, all the complexes showed better in vitro cytotoxic activity against MCF-7, Hop62, MDA-MB cell lines [79]. 7-Chloroquinoline thiosemicarbazone and its complexes of Ga(III), Cytotoxic and antimalarial activity were tested and proved that the complex shows 31 times better activity on colon cancer cell line than etoposide. The complex has better antimalarial activity against
2-Acetylpyridine-N(4)-Orthochlorophenyl thiosemicarbazone and their complexes of Ga(III), Sn(IV), Pd(II) and Pt(II) Cytotoxic activity was reported. The results indicate the ligands and metal complexes showed better cytotoxic activity [81]. (Z)-(2-((1,3-Diphenyl-1H-pyrazol-4-yl) methylene) and hydrazinyl)(pyridin-2-ylamino) methane-thiol thiosemicarbazones and their complexes of Mn(II), Co(II), Ni(II), Cu(II), Zn(II), Cd(II) Cd(II) and Zn(II) complexes had strong antioxidative property. Ni(II) complex shows excellent activity against HepG2 and MCF-7 cancer cell line [82]. Cd(II) and its complexes of 2-Acetylyuridine-N4-substituted thiosemicarbazones and their Cytotoxic activity against human breast cancer cell lines was tested and found that one of cadmium complexes has better activity than the cisplatin drug [83]. Bi(III) and its complexes of 2,6-Diacetylpyridine bis (4N-methylthiosemicarbazone) have much more anti-bacterial and anticancer activity than its parent ligand against
2-Pyridineformamide thiosemicarbazones, 2-formyl and 2-acetyl acetyl pyridine thiosemicarbazones and its complexes of Ga(III) antiproliferative activity were evaluated against human cancer cell lines (MCF-7, T24, A549 and mouse L-929). 2-acetyl pyridine thiosemicarbazone shows higher activity than others against all cancer cell lines [87]. Kowol et al. [72] studied the anticancer activity of 2-Acetylpyridine N, N-dimethyl TSC, 2-acetyl pyridine N-pyrrolidinyl TSC, acetyl pyrazine N, N-dimethyl TSC, acetyl pyrazine N-pyrrolidinyl and acetyl pyrazine-N-piperidinyl TSC and its complexes of Ga(III), Fe(III). Cytotoxic activity of the ligands was enhanced by the chelation with Ga(III) while weakening with Fe(III). Noblia et al. [88] reported cytotoxic activity of 5-Bromo salicylaldehyde semicarbazone; 2-Hydroxy-naphtalen-1-carboxaldehyde semicarbazone and their vanadium complexes. The results indicate that the complexes had selective activity against TK-10 cell line. Anticancer activity of ortho-Naphthaquinone thiosemicarbazone and its Cu(II),Ni(II), Pd(II) and Pt(II) complexes were tested against MCF7 human breast cancer cell lines and results revealed that chelation of metal ion into ligand was enhanced its activity [89]. Casas et al. reported the cytotoxic activity of Formylferrocene thiosemicarbazones and their Au(III) complexes were evaluated against HeLa cell lines and found that antiproliferative activity was similar to cisplatin, a commercial drug.
Arion et al. [90] reported cytotoxic activity of 2-Acetylpyridine 4 N-dimethyl TSC and its Ga(III) complex against human cancer cell lines SW480, SK-BR-3, and 41 M were tested and results revealed that complexes show slightly higher activity than ligand. Antiproliferative activity of Acenaphthenequinone thiosemicarbazone and its Ni(II), Fe(II), Cu(II), Zn(II)were reported and found that Cu(II) complex shows better antiproliferative activity than others. Perez et al. [91] tested the cytotoxic activity of p-Isopropyl benzaldehyde and methyl 2-pyridyl ketone thiosemicarbazones and their Zn(II), Cd(II) against various cell lines. Results indicate that zinc complex was proven as a more potent antitumor agent. Jayasree and Araindakshan [92] reported the antitumor activity of Acetoacetanilide thiosemicarbazone and its Mn(II), Zn(II), Cd(II), Co(II), Fe (IIII) complexes against Ehrlich Ascites tumor cells and found that metal complexes were more active than free ligand. Mohan et al. [93] studied the antitumor activity of 2,6-Diacetylpyridine bis(N4-azacyclic thio semicarbazones) and their Mn(II), Fe(III), Fe(II), Co(II), Ni(II), Cu(II), Zn(II), Pt(II) complexes against P 388 lymphocytic leukemia test system in mice shows that copper complex shows better activity than others.
4. Conclusions
From the above discussion it is concluded that in most of the studies the metal complexes show greater cytotoxic activity than the free ligands. In metal complexes most of the researchers found the activity of palladium and platinum complexes than other metal complexes. There is a gap between structure activity relationship between metal complexes and their activity towards specific species. Metal complexes of thiosemicarbazones shows great antiproliferative activity and destroys cell completely. Several derivatives of TSC and its metal complexes such as Pt(II), Pd(II), Cu(II), Fe(II), Ni(II), etc., shows excellent cytotoxic activity.
References
- 1.
Azarkish M, Akbari A, Sedaghat T, Simpson J. Heteroleptic complexes of Zn(II) based on 1-(5-bromo-2-hydroxybenzylidene)-4-phenylthiosemicarbazide: Synthesis, structural characterization, theoretical studies and antibacterial activity. Journal of Molecular Structure. 2017; 1134 :126-134 - 2.
Guveli S, Ozdemir N, Ulkuseven B, Bal-Demirci T. Divalent nickel complexes of thiosemicarbazone based on 5-bromosalicylaldehyde and triphenylphosphine: Experimental and theoretical characterization. Polyhedron. 2016; 113 :16-24 - 3.
Matesanz A, Tapia S, Souza P. First 3,5-diacetyl-1,2,4-triazol derived mono(thiosemicarbazone) and its palladium and platinum complexes: Synthesis, structure and biological properties. Inorganica Chimica Acta. 2016; 445 :62-69 - 4.
Indoria S, Lobana TS, Sood H, Arora DS, Hundal G, Jasinski JP. Synthesis, spectroscopy, structures and antimicrobial activity of mixed-ligand zinc(II) complexes of 5-nitro-salicylaldehyde thiosemicarbazones. New Journal of Chemistry. 2016; 40 :3642-3653 - 5.
Stacy AE, Palanimuthu D, Bernhardt PV, Kalinowski DS, Jansson PJ, Richardson DR. Zinc(II)–Thiosemicarbazone Complexes Are Localized to the Lysosomal Compartment Where They Transmetallate with Copper Ions to Induce Cytotoxicity. Journal of Medicinal Chemistry. 2016; 59 :4965-4984 - 6.
Nguyena HH, Phama QT, Phung QM, Le CD, Thi Ngoc TT, Pham O, et al. Synthesis structures and biological activities of Pd(II) and Pt(II) complexes with 1-picolinoyl-4-substituted thiosemicarbazones. Journal of Molecular Structure. 2022; 1269 :133871 - 7.
Balakrishnana N, Haribabu J, Malekshah RE, Swaminathan S, Balachandran C, Bhuvanesh N, et al. Effect of N -benzyl group in indole scaffold of thiosemicarbazones on the biological activity of their Pd(II) complexes: DFT, biomolecular interactions,in silico docking, ADME and cytotoxicity studies. Inorganica Chemica Acta. 2022;534 :120805 - 8.
Nyawade EA, Sibuyi NRS, Meyer M, Lalancette R, Onani MO. Synthesis, characterization and anticancer activity of new 2-acetyl-5-methyl thiophene and cinnamaldehyde thiosemicarbazones and their palladium(II) complexes. Inorganica Chemica Acta. 2021; 515 :120036 - 9.
Matesanz AI, Jimenez-Faraco E, Ruiz MC, Balsa LM, Ranninger CN, León IE, et al. Mononuclear Pd(II) and Pt(II) complexes with an α-N-heterocyclic thiosemicarbazone: Cytotoxicity, solution behaviour and interaction versus proven models from biological media. Inorganic Chemistry. 2018; Front,5 :73-83 - 10.
Muralisankar M, Basheer SM, Haribabu J, Bhuvanesh NSP, Karvembu R, Sreekanth A. An investigation on the DNA/protein binding, DNA cleavage and in vitro anticancer properties of SNO pincer type palladium(II) complexes with N-substituted isatin thiosemicarbazone ligands. Inorganic Chimica Acta. 2017; 466 :61-70 - 11.
Kalairasi G, Umadevi C, Shanmugapriya A, Kalaivani P, Dallemer F, Prabhakaran R. DNA(CT), protein (BSA) binding studies, anti-oxidant and cytotoxicity studies of new binuclear Ni(II) complexes containing 4(N)-substituted thiosemicarbazones. Inorganica Chimica Acta. 2016; 453 :547-558 - 12.
Matesanz AI, Albacete P, Souza P. Synthesis and characterization of new bioactive mono(thiosemicarbazone) ligand based on 3,5-diacetyl-1,2,4-triazone diketone and its palladium and platinum complexes. Polyhedron. 2016; 109 :161-165 - 13.
Ali AQ , Teoh SG, Salhin A, Eltayeb NE, Khadeer Ahamed MB, Abdul Majid AMS. Synthesis of platinum(II) complexes of isatin thiosemicarbazones derivatives: In Vitro anti-cancer and deoxyribose nucleic acid binding activities. Inorganica Chimica Acta. 2014; 416 :235-244 - 14.
Matesanz AI, Leitao I, Souza P. Palladium(II) and platinum(II) bis(thiosemicarbazone) complexes of the 2,6-diacetylpyridine series with high cytotoxic activity in cisplatin resistant A2780cisR tumor cells and reduced toxicity. Journal of Inorganic Biochemistry. 2013; 125 :26-31 - 15.
Ramachandran E, Raja DS, Rath NP, Natarajan K. Role of substitution at terminal nitrogen of 2-Oxo-1,2-dihydroquinoline-3-carbaldehyde thiosemicarbazones on the coordination behavior and structure and biological properties of their palladium(II) complexes. Inorganic Chemistry. 2013; 52 :1504-1514 - 16.
Ramachandran E, Raja DS, Bhuvanesh NSP, Nataraja K. Mixed ligand palladium (II) complexes of 6-methoxy-2-oxo-1,2-dihydroquinoline-3-carbaldehyde 4N-substituted thiosemicarbazones with triphenylphosphine co-ligand: Synthesis, crystal structure and biological properties. Dalton Transactions. 2012; 41 :13308-13323 - 17.
Castineiras A, Fernandez-Hermida N, Garcia-Santos I, Gomez-Rodriguez L. Neutral NiII, PdII and PtII ONS-pincer complexes of 5-acetylbarbituric-4Ndimethylthiosemicarbazone: Synthesis, characterization and properties. Dalton Transactions. 2012; 41 :13486-13495 - 18.
Matesanz AI, Hernandez C, Rodriguez A, Souza P. 3,5-Diacetyl-1,2,4-triazol bis(4N-substituted thiosemicarbazone) palladium(II) complexes: Synthesis, structure, anti-proliferative activity and low toxicity on normal kidney cells. Journal of Inorganic Biochemistry. 2011; 105 :1613-1622 - 19.
Matesanz AI, Hernandez C, Rodriguez A, Souza P. Novel bis(thiosemicarbazones) of the 3,5-diacetyl-1,2,4-triazol series and their platinum(II) complexes: Chemistry, antiproliferative activity and preliminary nephrotoxicity studies. Dalton Transactions. 2011; 40 :5738-5745 - 20.
Iyidogan AK, Tasdemir D, Oruc-Emre EE, Balzarini J. Novel platinum(II) and palladium(II) complexes of thiosemicarbazones derived from 5-substitutedthiophene-2-carboxaldehydes and their antiviral and cytotoxic activities. European Journal of Medicinal Chemistry. 2011; 46 :5616-5624 - 21.
Matesanz AI, Joie C, Souza P. Chemistry, antiproliferative activity and low nephron toxicity of 3,5-diacetyl-1,2,4-triazol bis(4N-thiosemicarbazone) ligands and their platinum(II) complexes. Dalton Transactions. 2010; 39 :7059-7065 - 22.
Maia PIDS, Graminha A, Pavan FR, Leite CQF, Batista AA, Back DF, et al. Palladium(II) complexes with thiosemicarbazones. Synthesis, characterization and cytotoxicity against breast cancer cells and anti- Mycobacterium tuberculosis activity. Journal of Brazilian Chemical Society. 2010;7 :1177-1186 - 23.
Matesanz AI, Souza P. Palladium and platinum 3,5-diacetyl-1,2,4-triazol bis (thiosemicarbazones): Chemistry, cytotoxic activity and structure-activity relationship. Journal of Inorganic Biochemistry. 2007; 101 :245-253 - 24.
Padhye S, Afrasiabi Z, Sinn E, Fok J, Mehta K, Rath N. Antitumor metallothiosemicarbazonates: Structure and antitumor activity of palladium complex of phenanthrenequinone thiosemicarbazone. Inorganic Chemistry. 2005; 44 :1154-1156 - 25.
Kovala-Demertzi D, Demertzis MA, Filiou E, Pantazaki AA, Yadav PN, Miller JR, et al. Platinum(II) and palladium(II) complexes with 2-acetyl pyridine 4N-ethyl thiosemicarbazone able to overcome the cis -platin resistance. Structure, antibacterial activity and DNA strand breakage. Biometals. 2003;16 :411-418 - 26.
Kovala-Demertzi D, Demertzis MA, Miller JR, Papadopoulou C, Dodorou C, Filousis G. Platinum(II) complexes with 2-acetyl pyridine thiosemicarbazone: Synthesis, crystal structure, spectral properties, antimicrobial and antitumour activity. Journal of Inorganic Biochemistry. 2001; 86 :555-563 - 27.
Kovala-Demertzi D, Yadav PN, Demertzis MA, Coluccia M. Synthesis, crystal structure, spectral properties and cytotoxic activity of platinum(II) complexes of 2-acetyl pyridine and pyridine-2-carbaldehyde N(4)-ethyl-thiosemicarbazones. Journal of Inorganic Biochemistry. 2000; 78 :347-354 - 28.
Kovala-Demertzi D, Miller JR, Kourkoumelis N, Hadjikakou SK, Demertzis MA. Palladium(II) and platinum(II) complexes of pyridine-2-carbaldehyde thiosemicarbazone with potential biological activity. Synthesis, structure and spectral properties. Extended network via hydrogen bon linkages of [Pd(PyTsc)Cl]. Polyhedron. 1999; 18 :1005-1013 - 29.
Matesanz AI, Perez JM, Navarro P, Moreno JM, Colacio E, Souza P. Synthesis and characterization of novel palladium(II) complexes of bis (thiosemicarbazone). Structure, cytotoxic activity and DNA binding of Pd(II)-benzyl bis(thiosemicarbazonate). Journal of Inorganic Biochemistry. 1999; 76 :29-37 - 30.
Quiroga AG, Perez JM, Lopez-Solera I, Montero EI, Masaguer JR, Alonso C, et al. Binuclear chloro-bridged palladated and platinated complexes derived from p-isopropylbenzaldehyde thiosemicarbazone with cytotoxicity against cisplatin resistant tumor cell lines. Journal of Inorganic Biochemistry. 1998; 69 :275-281 - 31.
Quiroga AG, Perez JM, Lopez-Solera I, Masaguer JR, Luque A, Roman P, et al. Novel tetranuclear orthometalated complexes of Pd(II) and Pt(II) derived from p-isopropylbenzaldehyde thiosemicarbazone with cytotoxic activity in cis-DDP resistant tumor cell lines. Interaction of these complexes with DNA. Journal of Medicinal Chemistry. 1998; 41 :1399-1408 - 32.
Quiroga AG, Perez JM, Montero EI, Masaguer JR, Alonso C, Navarro-Ranninger C. Palladated and platinated complexes derived from phenylacetaldehyde thiosemicarbazone with cytotoxic activity in cis-DDP resistant tumor cells. Formation of DNA interstrand cross-links by these complexes. Journal of Inorganic Biochemistry. 1998; 70 :117-123 - 33.
Kovala-Demertzi D, Domopoulou A, Demertzis MA, Valle G, Papageorgiou A. Palladium(II) complexes of 2-acetylpyridine N(4)-methyl, N(4)-ethyl and N(4)-phenyl-thio semicarbazones. Crystal structure of chloro(2-acetylpyridine N(4)-methylthiosemicarbazonato) palladium(II). Synthesis, spectral studies, in vitro andin vivo antitumor activity. Journal of Inorganic Biochemistry. 1997;68 :147-155 - 34.
Kovala-Demertzi D, Domopoulou A, Demertzis MA, Papageorgiou A, West DX. Palladium(II) complexes of 2-acetylpyridine N(4)-propyl, N(4)-dipropyl- and 3-hexa methyleneiminyl thiosemicarbazones with potentially interesting biological activity. Synthesis, spectral properties, antifungal and in vitro antitumor activity. Polyhedron. 1997; 16 (20):3625-3633 - 35.
Pósa V, Hajdu B, Tóth G, Dömötör O, Kowol CR, Bernhard KK, et al. The coordination modes of (thio)semicarbazone copper(II) complexes strongly modulate the solution chemical properties and mechanism of anticancer activity. Journal of Inorganic Biochemistry. 2022; 231 :111786 - 36.
Mathews NA, Kurup MRP. Copper(II) complexes as novel anticancer drug: Synthesis, spectral studies, crystal structures, in silico molecular docking and cytotoxicity. Journal of Molecular Structure. 2022;1258 :132672 - 37.
Adhikari HS, Garai A, Manandhar KD, Yadav PN. Pyridine-based NNS tridentate chitosan thiosemicarbazones and their copper(II) complexes: Synthesis, characterization, and anticancer activity. ACS. 2022; 7 (35):30978-30988 - 38.
Haribabu J, Alajrawy OI, Jeyalakshmi K, Balachandran C, Anantha Krishnan D, Bhuvanesh N, et al. N -substitution in isatin thiosemicarbazones decides nuclearity of Cu(II) complexes – Spectroscopic, molecular docking and cytotoxic studies. Spectrochemica Acta Part A: Molecular and Bimolecular Spectroscopy. 2021;246 :118963 - 39.
Pitucha M, Plewko AK, Czylkowska A, Rogalewicz B, Drozd M, Iwan M, et al. Influence of complexation of thiosemicarbazone derivatives with Cu (II) ions on their antitumor activity against melanoma cells. International Journal of Molecular Sciences. 2021, 2021; 22 (6):3104 - 40.
Gatto CC, Chagas MAS, Lima IJ, Andrade FM, Silva HD, Abrantes GR, et al. Copper(II) complexes with pyridoxal dithiocarbazate and thiosemicarbazone ligands: Crystal structure, spectroscopic analysis and cytotoxic activity. Transition Metal Chemistry. 2019; 44 :329-340 - 41.
Aneesrahman KN, Rohini G, Bhuvanesh NSP, Sundararaj S, Musthafa M, Sreekanth A. In vitro biomolecular interaction studies and cytotoxic activities of newly synthesised copper(II) complexes bearing 2-hydroxynaphthaldehyde-based thiosemicarbazone. Chemistry Select. 2019; 3 (28), 2018:8118-8130 - 42.
Zou BQ , Lu X, Qin QP, Bai YX, Zhang Y, Wang M, et al. Three novel transitional metal complexes of 6-methyl-2-oxo-quinoline-3-carbaldehyde thiosemicarbazone: Synthesis, crystal structure, cytotoxicity and mechanism of action. RSC Advances. 2017; 7 :17923-17933 - 43.
Da Silva JG, Despaigne AAR, Louro SRW, Bandeira CC, Souza-Fagundes EM, Beraldo H. Cytotoxic activity, albumin and DNA binding of new copper(II) complexes with chalcone-derived thiosemicarbazones. European Journal of Medicinal Chemistry. 2013; 65 :415-426 - 44.
Palanimuthu D, Shinde SV, Somasundaram K, Samuelson AG. In vitro and in vivo anticancer activity of copper bis(thiosemicarbazone) complexes. Journal of Medicinal Chemistry. 2013; 56 :722-734 - 45.
Raja DS, Bhuvanesh NSP, Natarajan K. Biological evaluation of a novel water soluble sulphur bridged binuclear copper(II) thiosemicarbazone complex. European Journal of Medicinal Chemistry. 2011; 46 :4584-4594 - 46.
Raja DS, Paramaguru G, Bhuvanesh NSP, Reibenspies JH, Renganathan R, Natarajan K. Effect of terminal N-substitution in 2-oxo-1,2-dihydroquinoline-3-carbaldehyde thiosemicarbazones on the mode of coordination, structure, interaction with protein, radical scavenging and cytotoxic activity of copper(II) complexes. Dalton Transactions. 2011; 40 :4548-4559 - 47.
Zeglis BM, Divilov V, Lewis JS. Role of metalation in the topoisomerase IIα inhibition and antiproliferation activity of a series of α-heterocyclic-N4-substituted thiosemicarbazones and their Cu(II) complexes. Journal of Medicinal Chemistry. 2011; 54 :2391-2398 - 48.
Jansson PJ, Sharpe PC, Bernhardt PV, Richardson DR. Novel thiosemicarbazones of the ApT and DpT series and their copper complexes: Identification of pronounced redox activity and characterization of their antitumor activity. Journal of Medicinal Chemistry. 2010; 53 :5759-5769 - 49.
Rosu T, Pahontu E, Pasculescu S, Gerogescu R, Stanica N, Curaj A, et al. Synthesis, characterization antibacterial and antiproliferative activity of novel Cu(II) and Pd(II) complexes with 2-hydroxy-8-R-tricyclo[7.3.1.0.2,7] tridecane-13-one thiosemicarbazone. European Journal of Medicinal Chemistry. 2010; 45 :1627-1634 - 50.
Patole J, Padhye S, Padhye S, Newton CJ, Anson C, Powell AK. Synthesis, characterization and in vitro anti-cancer activities of semicarbazone and thiosemicarbazone derivatives of salicylaldehyde and their complexes against human breast cancer cell line MCF-7. Indian Journal of Chemistry. 2004; 43A :1654-1658 - 51.
Baldini M, Belicchi-Ferrari M, Bisceglie F, Pelosi G, Pinelli S, Tarasconi P. Cu(II) complexes with heterocyclic substituted thiosemicarbazones: The case of 5-formyluracil. Synthesis, characterization, X-ray structures, DNA interaction studies, and biological activity. Inorganic Chemistry. 2003; 42 :2049-2055 - 52.
Belicchi-Ferrari M, Bisceglie F, Fava GG, Pelosi G, Tarasconi P, Albertini R, et al. Synthesis, characterization and biologically activity of two new polymeric copper(II) complexes with α-Ketoglutaric acid thiosemicarbazone. Journal of Inorganic Biochemistry. 2002; 89 :36-44 - 53.
Murugkar A, Padhye S, Roy SG, Wagh U. Metal complexes of Taxol precursor 1. Synthesis, characterization and antitumor activity of the copper complex of 10-deacetylbaccatin thiosemicarbazone. Inorganic Chemistry Communications. 1999; 2 :545-548 - 54.
Miller MC, Stineman CN, Vance JR, West DX, Hall IH. Multiple mechanisms for cytotoxicity induced by copper(II) complexes of 2-acetylpyrazine-N-substituted thiosemicarbazones. Applied Organometallic Chemistry. 1999; 13 :9-19 - 55.
Belicchi Ferrari M, Fava GG, Leporati E, Pelosi G, Rossi R, Tarasconi P, et al. Synthesis, characterization and biological activity of three copper(II) complexes with a modified nitrogenous base: 5-formyluracil thiosemicarbazone. Journal of Inorganic Biochemistry. 1998; 70 :145-154 - 56.
Rogolino D, Cavvvazzoni A, Gatti A, Tegoni M, Pelosi G, Verdolino V, et al. Anti-proliferative effects of copper(II) complexes with hydroxyquinoline-thiosemicarbazone ligands. European Journal of Medicinal Chemistry. 2017; 128 :140-153 - 57.
Belicchi Ferrari M, Bisceglie F, Pelosi G, Tarasconi P, Albertini R, Pinelli S. New methyl pyruvate thiosemicarbazones and their copper and zinc complexes: Synthesis, characterization, X-ray structures and biological activity. Journal of Inorganic Biochemistry. 2001; 87 :137-147 - 58.
Muralisankar M, Haribabu J, Bhuvanesh NSP, Karvembu R, Sreekanth A. Synthesis, X-ray crystal structure, DNA/protein binding, DNA cleavage and cytotoxic studies of N(4) substituted thiosemicarbazone based copper(II)/nickel(II) complexes. Inorganica Chimica Acta. 2016; 449 :82-95 - 59.
Jagadeesh M, Lavanya M, Kalangi SK, Sarala Y, Ramachandraiah C, Varada Reddy A. Spectroscopic characterization, antioxidant and antitumor studies of novel bromo substituted thiosemicarbazone and its copper(II), nickel(II), and palladium(II) complexes. Spectrochimica Acta Part A. 2015; 135 :180-184 - 60.
Bisceglie F, Pinelli S, Alinovi R, Goldoni M, Mutti A, Camerini A, et al. Cinnamaldehyde and cuminaldehyde thiosemicarbazones and their copper (II) and nickel(II) complexes: A study to understand their biological activity. Journal of Inorganic Biochemistry. 2014; 140 :111-125 - 61.
Jagadeesh M, Kalangi SK, Krishna LS, Varada Reddy A. Halo-substituted thiosemicarbazones and their copper(II), nickel(II) complexes: Detailed spectroscopic characterization and study of antitumor activity against HepG2 human hepatoblastoma cells. Spectrochimica Acta Part A. 2014; 118 :552-556 - 62.
Shao J, Ma ZY, Li A, Liu YH, Xie CZ, Qiang ZY, et al. Thiosemicarbazone Cu(II) and Zn(II) complexes as potential anticancer agents: Syntheses, crystal structure, DNA cleavage, cytotoxicity and apoptosis induction activity. Journal of Inorganic Biochemistry. 2014; 136 :13-26 - 63.
Pelosi G, Bisceglie F, Bignami F, Ronzi P, Schiavone P, Carla Re M, et al. Antiretroviral activity of thiosemicarbazone metal complexes. Journal of Medicinal Chemistry. 2010; 53 :8765-8769 - 64.
Md Yusof EN, Ravoof TBSA, Tiekink ERT, Veerrakumarasivam A, Crouse KA, Mohamed Tahir MI, et al. Synthesis, characterization and biological evaluation of transition metal complexes derived from N,S bidentate ligands. International Journal of Molecular Sciences. 2015; 16 :11034-11054 - 65.
Selvamurugan S, Ramachandran R, Vijayan P, Manikandan R, Prakash G, Viswanatha murthi, P., Velmururgan, K., Nandhakumar, R., Endo, A. Synthesis, crystal structure and biological evaluation of Ni(II) complexes containing 4-chromone- N (4)-substituted thiosemicarbazone ligands. Polyhedron. 2016;107 :57-67 - 66.
Palanimuthu D, Samuelson AG. Dinuclear zinc bis(thiosemicarbazone) complexes: Synthesis, in vitro anticancer activity, cellular uptake and DNA interaction study. Inorganica Chimica Acta. 2013; 408 :152-161 - 67.
Prabhakaran R, Kalaivani P, Huang R, Poornima P, Padma VV, Dallemer F, et al. DNA binding, antioxidant, cytotoxicity (MTT, lactate dehydrogenase, NO), and cellular uptake studies of structurally different nickel(II) thiosemicarbazone complexes: Synthesis, spectroscopy, electrochemistry, and X-ray crystallography. Journal of Biological Inorganic Chemistry. 2013; 18 :233-247 - 68.
Afrasiabi Z, Sinn E, Lin W, Ma Y, Campana C, Padhye S. Nickel(II) complexes of naphthaquinone thiosemicarbazone and semicarbazone: Synthesis, structure, spectroscopy, and biological activity. Journal of Inorganic Biochemistry. 2005; 99 :1526-1531 - 69.
Belicchi Ferrari M, Capacchi S, Reffo G, Pelosi G, Tarasconi P, Albertini R, et al. Synthesis, structural characterization and biological activity of p -fluoro benzaldehyde thiosemicarbazones and of a nickel complex. Journal of Inorganic Biochemistry. 2000;81 :89-97 - 70.
Gou Y, Wang J, Chen S, Zhang Z, Zhang Y, Zhang W, et al. α-N-heterocyclic thiosemicarbazone Fe(III) complex: Characterization of its antitumor activity and identification of anticancer mechanism. European Journal of Medicinal Chemistry. 2016; 123 :354-364 - 71.
Richardson DS, Kallinowshi DS, Richardson V, Sharpe PC, Lovejoy DB, Islam M, et al. 2-Acetylpyridine thiosemicarbazones are potent iron chelators and antiproliferative agents: Redox activity, iron complexation and characterization of their antitumor activity. Journal of Medicinal Chemistry. 2009; 52 :1459-1470 - 72.
Kowol CR, Berger R, Eichinger R, Roller A, Jakupec MA, Schmidt PP, et al. Gallium(III) and iron(III) complexes of α-N-heterocyclic thiosemicarbazones: Synthesis, characterization, cytotoxicity, and interaction with ribonucleotide reductase. Journal of Medicinal Chemistry. 2007; 50 :1254-1265 - 73.
Richardson DR, Sharpe PC, Lovejoy DB, Senaratne D, Kalinowski DS, Islam M, et al. Dipyridyl thiosemicarbazone chelators with potent and selective antitumor activity form iron complexes with redox activity. Journal of Medicinal Chemistry. 2006; 49 :6510-6521 - 74.
Mohan M, Kumar M, Kumar A, Madhuranath PH, Jha NK. Synthesis, characterization, and antitumour activity of iron(II) and iron(III) complexes of α-heterocyclic carboxaldehyde thiosemicarbazones. Journal of Inorganic Biochemistry. 1988; 32 :239-249 - 75.
Salam MA, Hussein MA, Ramli I, Islam MS. Synthesis, structural characterization and evaluation of biological activity of organotin(IV) complexes with 2-hydroxy-5-methoxy benzaldehyde-N(4)-methylthiosemicarbazone. Journal of Organometallic Chemistry. 2016; 813 :71-77 - 76.
Li MX, Zhang D, Zhang LZ, Niu JY, Ji BS. Diorganotin(IV) complexes with 2-benzoylpyridine and 2-acetylpyrazine N(4)-phenylthiosemicarbazones: Synthesis, crystal structures and biological activities. Journal of Organometallic Chemistry. 2011; 696 :852-858 - 77.
Casas JS, Rodriguez-Arguelles MC, Russo U, Sanchez A, Sordo J, Vazquez-Lopez A, et al. Diorganotin(IV) complexes of pyridoxal thiosemicarbazone: Synthesis, spectroscopic properties and biological activity. Journal of Inorganic Biochemistry. 1998; 69 :283-292 - 78.
Tai YX, Ji YM, Lu YL, Li MX, Wu YY, Han QX. Cadmium(II) and indium(IIII) complexes derived from 2-benzoylpyridine N (4)-cyclohexylthiosemicarbazone: Synthesis, crystal structures, spectroscopic characterization and cytotoxicity. Synthetic Metals. 2016;219 :109-114 - 79.
Vijayan P, Viswanathamurthi P, Silambarasan V, Velmurugan D, Velmurugan K, Nandhakumar R, et al. Dissymmetric thiosemicarbazone ligands containing substituted aldehyde arm and their ruthenium(II) carbonyl complexes with PPh3/AsPh3 as ancillary ligands: Synthesis, structural characterization, DNA/BSA interaction and in vitro anticancer activity. Journal of Organometallic Chemistry. 2014; 768 :163-177 - 80.
Kumar K, Schniper S, Gonzalez-Sarrias A, Holder AA, Sanders N, Sullivan D, et al. Highly potent anti-proliferative effects of a gallium(III) complex with 7-chloroquinoline thiosemicarbazone as a ligand: Synthesis, cytotoxic and antimalarial evaluation. European Journal of Medicinal Chemistry. 2014; 86 :81-86 - 81.
Parrilha GL, Ferraz KSO, Lessa JA, Navakoski de Oliveira K, Rodrigues BL, Ramos JP, et al. Metal complexes with 2-acetylpyridine-N(4)-orthochlorophenylthiosemicarbazone: Cytotoxicity and effect on the enzymatic activity of thioredoxin reductase and glutathione reductase. European Journal of Medicinal Chemistry. 2014; 84 :537-544 - 82.
Yousef TA, Abu El-Reash GM, Al-Jahdali M, El-Rakhawy EBR. Synthesis, spectral characterization and biological evaluation of Mn(II), Co(II), Ni(II), Cu(II), Zn(II) and Cd(II) complexes with thiosemicarbazone ending by pyrazole and pyridyl rings. Spectrochimica Acta Part A. 2014; 129 :163-172 - 83.
Manikandan R, Chitrapriya N, Jang YJ, Viswanathamurthi P. Evaluation of DNA-binding, radical scavenging and cytotoxic activity of five coordinated Cd(II) complexes containing 2-acetylpyridine-N4-substituted thiosemicarbazone. RSC Advances. 2013; 3 :11647-11657 - 84.
Li MX, Yang M, Niu JY, Zhang LZ, Xie SQ. A nine-coordinated bismuth(III) complex derived from pentadentate 2,6-diacetyl pyridine bis(4N-methylthiosemicarbazone): Crystal structure and both in vitro and in vivo biological evaluation. Inorganic Chemistry. 2012; 51 :12521-12526 - 85.
Stringer T, Therrien B, Hendricks DT, Guzgay H, Smith GS. Mono- and dinuclear (η6-arene) ruthenium(II) benzaldehyde thiosemicarbazone complexes: Synthesis, characterization and cytotoxicity. Inorganic Chemistry Communications. 2011; 14 :956-960 - 86.
Li MX, Chen CL, Zhang D, Niu JY, Ji BS. Mn(II), Co(II) and Zn(II) complexes with heterocyclic substituted thiosemicarbazones: Synthesis, characterization, X-ray crystal structures and antitumor comparison. European Journal of Medicinal Chemistry. 2010; 45 :3169-3177 - 87.
Kovala-Demertzi D, Papageorgiou A, Papathanasis L, Alexandratos A, Dalezis P, Miller JR, et al. In vitro and in vivo antitumor activity of platinum(II) complexes with thiosemicarbazones derived from 2-formyl and 2-acetyl pyridine and containing ring incorporated at N(4)-position: Synthesis, spectroscopic study and crystal structure of platinum(II) complexes with thiosemicarbazones, potential anticancer agents. European Journal of Medicinal Chemistry. 2009; 44 :1296-1302 - 88.
Noblia P, Vieites M, Parajon-Costa BS, Baran EJ, Cerecetto H, Draper P, et al. Vanadium(V) complexes with salicylaldehyde semicarbazone derivatives bearing in vitro anti-tumor activity toward kidney tumor cells (TK-10): Crystal structure of [VVO2(5-bromosalicylaldehde semicarbazone)]. Journal of Inorganic Biochemistry. 2005; 99 :443-451 - 89.
Afrasiabi Z, Sinn E, Chen J, Ma Y, Rheingold AL, Zakharov LN, et al. Appended 1,2-naphthoquinones as anticancer agents 1: Synthesis, structural, spectral and antitumor activities of ortho-naphthaquinone thiosemicarbazone and its transition metal complexes. Inorganica Chimica Acta. 2004; 357 :271-278 - 90.
Arion VB, Jakupec MA, Galanski M, Unfried P, Keppler BK. Synthesis, structure, spectroscopic and in vitro antitumor studies of a novel gallium(III) complex with 2-acetyl pyridine 4N-dimethylthiosemicarabzone. Journal of Inorganic Biochemistry. 2002; 91 :298-305 - 91.
Perez JM, Matesanz AI, Ambite AM, Navarro P, Alonso C, Souza P. Synthesis and characterization of complexes of p -isopropyl benzaldehyde and methyl 2-pyridyl ketone thiosemicarbazones with Zn(II) and Cd(II) metallic centers. Cytotoxic activity and induction of apoptosis in Pam-ras cells. Journal of Inorganic Biochemistry. 1999;75 :255-261 - 92.
Jayasree S, Aravindakshan KK. Synthesis, characterization and antitumour studies of metal chelates of acetoacetanilide thiosemicarbazone. Transition Metal Chemistry. 1993; 18 :85-88 - 93.
Mohan M, Agarawal A, Jha NK. Synthesis, characterization and antitumour properties of some metal complexes of 2,6-diacetylpyridine bis(N4-azacyclic thiosemicarbazones). Journal of Inorganic Biochemistry. 1988; 34 :41-54