title: Antifungal effect of 4-arylthiosemicarbazides against Candida species. Search for molecular basis of antifungal activity of thiosemicarbazide derivatives.
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.
authors.affiliation: Department of Organic Chemistry, Faculty of Pharmacy, Medical University, Chodźki 4a, 20-093, Lublin, Poland. agata.siwek@am.lublin.pl
authors.forename: Agata
authors.initials: A
authors.lastname: Siwek
authors.forename: Joanna
authors.initials: J
authors.lastname: Stefańska
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Dzitko
authors.forename: Artur
authors.initials: A
authors.lastname: Ruszczak
mesh_terms: D000217:Acyltransferases / Q000037:antagonists & inhibitors / Q000737:chemistry; D000818:Animals; D000935:Antifungal Agents / Q000737:chemistry* / Q000494:pharmacology*; D002175:Candida / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D020134:Catalytic Domain; D016923:Cell Death / Q000187:drug effects; D002460:Cell Line; D008024:Ligands; D051379:Mice; D008826:Microbial Sensitivity Tests; D008968:Molecular Conformation; D062105:Molecular Docking Simulation; D012663:Semicarbazides / Q000737:chemistry / Q000494:pharmacology*; D013045:Species Specificity; D055672:Static Electricity; D013816:Thermodynamics
chemical_list: D000935:Antifungal Agents; D008024:Ligands; D012663:Semicarbazides; C005151:thiosemicarbazide; D000217:Acyltransferases; C050480:glycylpeptide N-tetradecanoyltransferase