1. Antifungal effect of 4-arylthiosemicarbazides against Candida species. Search for molecular basis of antifungal activity of thiosemicarbazide derivatives
- Author
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Agata Siwek, Katarzyna Dzitko, Joanna Stefańska, and Artur Ruszczak
- Subjects
Antifungal Agents ,Molecular model ,Stereochemistry ,Cytotoxicity ,Static Electricity ,Molecular Conformation ,Microbial Sensitivity Tests ,Ligands ,Catalysis ,Cell Line ,Inorganic Chemistry ,chemistry.chemical_compound ,Mice ,Species Specificity ,Catalytic Domain ,Structure–activity relationship ,Animals ,Antifungal activity ,Isoquinoline ,Physical and Theoretical Chemistry ,Glutamine amidotransferase ,Candida ,chemistry.chemical_classification ,DNA ligase ,Original Paper ,biology ,Cell Death ,Ligand ,Topoisomerase ,Organic Chemistry ,Thiosemicarbazide derivative ,Structure-activity relationship ,Computer Science Applications ,Semicarbazides ,Molecular Docking Simulation ,Biochemistry ,chemistry ,Computational Theory and Mathematics ,Docking (molecular) ,Molecular docking ,biology.protein ,Thermodynamics ,Acyltransferases - Abstract
The in vitro antifungal potency of six series of 4-arylthiosemicarbazides was evaluated. Two isoquinoline derivatives with an ortho-methoxy or ortho-methyl group at the phenyl ring were the most potent antifungal agents. Molecular modeling studies and docking of all 4-arylthiosemicarbazides into the active sites of sterol 14α-demethylase (CYP51), topoisomerase II (topo II), l-glutamine: d-fructose-6-phosphate amidotransferase (GlcN-6-P), secreted aspartic proteinase (SAP), N-myristoyltransferase (NMT), and UDP-N-acetylmuramoyl-l-alanine:d-glutamate ligase (MurD) indicated the importance of both structural and electronic factors in ligand recognition and thus for the antifungal effectiveness of 4-arylthiosemicarbazides. A possible antifungal target was identified (NMT) and isoquinoline-thiosemicarbazides showed more favorable affinity than the native ligand. Figure Electrostatic potential surface of isoquiniline derivative compound 6o with antifungal activity Electronic supplementary material The online version of this article (doi:10.1007/s00894-012-1420-5) contains supplementary material, which is available to authorized users.
- Published
- 2012