Antifungal effect of 4-arylthiosemicarbazides against Candida species. Search for molecular basis of antifungal activity of thiosemicarbazide derivatives |
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Authors: | Agata Siwek Joanna Stefańska Katarzyna Dzitko Artur Ruszczak |
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Institution: | Department of Organic Chemistry, Faculty of Pharmacy, Medical University, Chod?ki 4a, 20-093, Lublin, Poland. agata.siwek@am.lublin.pl |
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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. |
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