Antifungal effect of 4-arylthiosemicarbazides against Candida species. Search for molecular basis of antifungal activity of thiosemicarbazide derivatives
Open Access
- 26 April 2012
- journal article
- research article
- Published by Springer Science and Business Media LLC in Journal of Molecular Modeling
- Vol. 18 (9), 4159-4170
- https://doi.org/10.1007/s00894-012-1420-5
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. Electrostatic potential surface of isoquiniline derivative compound 6o with antifungal activityKeywords
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