Title:Search for Molecular Basis of Antifungal Activity of Thiosemicarbazide Derivatives: A Combined in vitro Antifungal and Enzymatic Studies with in Silico Docking
VOLUME: 10 ISSUE: 1
Author(s):Agata Siwek, Pawel Staczek, Aleksandra Strzelczyk and Joanna Stefanska
Affiliation:Department of Organic Chemistry, Faculty of Pharmacy, Medical University, Chodzki 4a, 20-093 Lublin, Poland.
Keywords:Antifungal activity, Modeling prediction, Molecular docking, Thiohydantoine, Thiosemicarbazide, s-triazole, Candida albicans, MIC range, GNAT, N-acetyltransferase
Abstract:In this study, a combined in vitro antifungal and enzymatic studies with molecular modeling techniques are
presented. Although attempts with rational design strategies have been made, the bioactivity of studied 1-substituted 4-
ethoxycarbonylmethylthiosemicarbazides 1a-1g was only marginal. Among the compounds tested, antifungal response
was observed only for indole derivative 1f and pyrazine derivative 1g. The most important results of the antifungal
screening assay can be summarized as follows: (i) the replacement of an aryl ring in 4-arylthiosemicarbazides with a
flexible chain reduces antifungal response dramatically, (ii) NH-NH-C(=S)-NH core seems to be important for antifungal
activity of thiosemicarbazides. Based on docking simulations fungal secreted aspartic proteinase (SAP) was proposed as
the putative enzyme target for thiosemicarbazide derivatives with a flexible chain at the N4 position of thiosemicarbazide
core.
