Antifungal effect of 4-arylthiosemicarbazides against Candida species. Search for molecular basis of antifungal activity of thiosemicarbazide derivatives

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...

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Bibliographic Details
Published in:Journal of molecular modeling 2012-09, Vol.18 (9), p.4159-4170
Main Authors: Siwek, Agata, Stefańska, Joanna, Dzitko, Katarzyna, Ruszczak, Artur
Format: Article
Language:English
Subjects:
Acyltransferases - antagonists & inhibitors
Acyltransferases - chemistry
Animals
Antifungal Agents - chemistry
Antifungal Agents - pharmacology
Candida
Candida - cytology
Candida - drug effects
Candida - enzymology
Catalytic Domain
Cell Death - drug effects
Cell Line
Characterization and Evaluation of Materials
Chemistry
Chemistry and Materials Science
Computer Appl. in Life Sciences
Computer Applications in Chemistry
Ligands
Mice
Microbial Sensitivity Tests
Molecular Conformation
Molecular Docking Simulation
Molecular Medicine
Original Paper
Semicarbazides - chemistry
Semicarbazides - pharmacology
Species Specificity
Static Electricity
Theoretical and Computational Chemistry
Thermodynamics
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Summary: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
ISSN:1610-2940
0948-5023
DOI:10.1007/s00894-012-1420-5