New Benzimidazole-124-Triazole Hybrid Compounds: Synthesis Anticandidal Activity and Cytotoxicity Evaluation

摘要

Owing to the growing need for antifungal agents, we synthesized a new series 2-((5-(4-(5-substituted-1H-benzimidazol-2-yl)phenyl)-4-substituted-4H-1,2,4-triazol-3-yl)thio)-1-(substitutedphenyl)ethan-1-one derivatives, which were tested against Candida species. The synthesized compounds were characterized and elucidated by FT-IR, ¹H-NMR, ¹³C-NMR and HR-MS spectroscopies. The synthesized compounds were screened in vitro anticandidal activity against Candida species by broth microdiluation methods. In vitro cytotoxic effects of the final compounds were determined by MTT assay. Microbiological studies revealed that compounds >5m, >5o, >5r, >5t, >5y, >5ab, and >5ad possess a good antifungal profile. Compounds >5w was the most active derivative and showed comparable antifungal activity to those of reference drugs ketoconazole and fluconazole. Cytotoxicity evaluation of compounds >5m, >5o, >5r, >5w, >5y, >5ab and >5ad showed that compounds >5w and >5ad were the least cytotoxic agents. Effects of these two compounds against ergosterol biosynthesis were observed by LC-MS-MS method, which is based on quantification of ergosterol level in C. albicans. Compounds >5w and >5d inhibited ergosterol biosynthesis concentration dependently. A fluorescence microscopy study was performed to visualize effect of compound >5w against C. albicans at cellular level. It was determined that compound >5w has a membrane damaging effect, which may be related with inhibition of biosynthesis of ergosterol.