Antifungal, cytotoxic activities and docking studies of 2,5-dimercapto-1,3,4-thiadiazole derivatives

A series of 2,5-dimercapto-1,3,4-thiadiazole derivatives (compounds 1 to 10) were prepared by nucleophilic substitution reaction between 2,5-dimercapto-1,3,4-thiadiazole and chloroheterocyclic compounds in methanol and in the presence of potassium carbonate (compounds 1 to 5 and 8) or metallic sodium (compounds 6, 7, 9 and 10) at room temperature. The cytotoxic activity was determined by green fluorescent protein (GFP)-based assay and anti-candida activity was determined by resazurin microplate assay (REMA). Compounds 1 to 4, 8 and 9 showed in vitro cytotoxic activities against Vero cells (African green monkey kidney). Compounds 4 and 10 exhibited anti-candida activities against Candida albicans (ATCC 90028) with IC50 values of 1.94 and 19.10 µg/ml, respectively. Docking studies on the catalytic site of cytochrome P450 14a-demethylase were used to identify the chemical structures in the molecule responsible for cytotoxic and anti-candida activities of the synthesized compounds.   Key words: 2,5-dimercapto-1,3,4-thiadiazol, docking, cytotoxicity, antifungal.