A novel series of thiazolyl-pyrazoline derivatives: synthesis and evaluation of antifungal activity, cytotoxicity and genotoxicity.

Abstract

In the current work, new thiazolyl-pyrazoline derivatives (1-22) were synthesized and evaluated for their antifungal effects against pathogenic yeasts and molds using a broth microdilution assay. Ames assay was carried out to determine the genotoxicity of the most effective antifungal derivatives. The cytotoxicity of the compounds (1-22) was also investigated against A549 human lung adenocarcinoma and NIH/3T3 mouse embryonic fibroblast cells. Among these derivatives, 2-[5-(4-fluorophenyl)-3-(5-methylthiophen-2-yl)-4,5-dihydro-1H-pyrazol-1-yl]-4-(4-methylsulfonylphenyl)thiazole (18) can be identified as the most promising anticandidal derivative due to its notable inhibitory effect on Candida zeylanoides with a MIC value of 250μg/mL when compared with ketoconazole (MIC=250μg/mL), low cytotoxicity against NIH/3T3 cells and non-mutagenic effect. On the other hand, 2-[5-(4-fluorophenyl)-3-(5-chlorothiophen-2-yl)-4,5-dihydro-1H-pyrazol-1-yl]-4-(4-bromophenyl)thiazole (4) can be considered as the most promising anticancer agent against A549 cancer cells owing to its notable inhibitory effect on A549 cells with an IC50 value of 62.5μg/mL when compared with cisplatin (IC50=45.88μg/mL) and low cytotoxicity against NIH/3T3 cells.