Chapters authored
Molecular Informatics of Trypanothione Reductase of Leishmania major Reveals Novel Chromen-2-One Analogues as Potential Leishmanicides
Trypanothione reductase (TR), a flavoprotein oxidoreductase is an important therapeutic target for leishmaniasis. Ligand-based pharmacophore modelling and molecular docking were used to predict selective inhibitors against TR. Homology modelling was employed to generate a three-dimensional structure of Leishmania major trypanothione reductase (LmTR). A pharmacophore model used to screen a natural compound library generated 42 hits, which were docked against the LmTR protein. Compounds with lower binding energies were evaluated via in silico pharmacological profiling and bioactivity. Four compounds emerged as potential leads comprising Karatavicinol (7-[(2E,6E,10S)-10,11-dihydroxy-3,7,11-trimethyldodeca-2,6-dienoxy]chromen-2-one), Marmin (7-[(E,6R)-6,7-dihydroxy-3,7-dimethyloct-2-enoxy]chromen-2-one), Colladonin (7-[[(4aS)-6-hydroxy-5,5,8a-trimethyl-2-methylidene-3,4,4a,6,7,8-hexahydro-1H-naphthalen-1-yl]methoxy]chromen-2-one), and Pectachol (7-[(6-hydroxy-5,5,8a-trimethyl-2-methylidene-3,4,4a,6,7,8-hexahydro-1H-naphthalen-1-yl)methoxy]-6,8-dimethoxychromen-2-one) with good binding energies of −9.4, −9.3, 8.8, and −8.5 kcal/mol, respectively. These compounds bound effectively to the FAD domain of the protein with some critical residues including Asp35, Thr51, Lys61, Tyr198, and Asp327. Furthermore, molecular dynamics simulations and molecular mechanics Poisson-Boltzmann surface area (MMPBSA) computations corroborated their strong binding. The compounds were also predicted to possess anti-leishmanial activity. The molecules serves as templates for the design of potential drug candidates and can be evaluated in vitro with optimistic results in producing plausible attenuating infectivity in macrophages.
Part of the book: Leishmaniasis
Honey as a Natural Product Worthy of Re-Consideration in Treating MRSA Wound Infections
The use of antibiotics to treat bacterial infections have largely been successful. However, the misuse and overuse of these precious drugs have led to the development of bacterial resistance and this seems to have jeopardized their effectiveness. Many antibiotics that hitherto were seen as “miraculous drugs”, have witnessed a low efficacy and this has threatened the life of humanity as never before. The rapid emergence of antibiotic resistance in bacteria is the major cause of this sad development. One such superbug is methicillin-resistant Staphylococcus aureus (MRSA). MRSA is a general problem in most healthcare centers with a reported astronomical incidence of invasive MRSA infections causing death. Honey, a natural product, popular for its antibacterial activity is increasingly being used owing to its reported antibiotic potential against ‘stubborn’ bacteria. This review discusses the fact that though honey is an ancient remedy, it is still relevant and its application in modern medicine for the treatment of chronically infected wounds caused by MRSA should be re-visited. Furthermore, the in vitro antibacterial and antibiofilm activities of medical-grade honey on S. aureus infections and challenges encountered by Researchers in developing honey, into an acceptable medical, therapeutic antibacterial agent for wound care have also been highlighted.
Part of the book: The Global Antimicrobial Resistance Epidemic