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Synthesis of Benzimidazole-1,2,4-triazole Derivatives as Potential Antifungal Agents Targeting 14α-Demethylase

Invasive fungal infections (IFIs) are increasing as major infectious diseases around the world, and the limited efficacy of existing medications has resulted in substantial morbidity and death in patients due to the lack of effective antifungal agents and serious drug resistance. In this study, a series of benzimidazole-1,2,4-triazole derivatives (6a-6l) were synthesized and characterized by 1H NMR, 13C NMR, and HR-MS spectral analysis. All the target compounds were screened for their in vitro antifungal activity against four fungal strains, namely, C. albicans, C. glabrata, C. krusei, and C. parapsilopsis. The synthesized compounds exhibited significant antifungal potential, especially against C. glabrata. Three compounds (6b, 6i, and 6j) showed higher antifungal activity with their MIC values (0.97 μg/mL) compared with voriconazole and fluconazole. Molecular docking provided a possible binding mode of compounds 6b, 6i, and 6j in the 14α-demethylase active site. Our studies suggested that the benzimidazole-1,2,4-triazole derivatives can be used as a new fungicidal lead targeting 14α-demethylase for further structural optimization. In addition, their effects on the L929 cell line were also investigated to evaluate the cytotoxic effects of the compounds. SEM analyses were performed to examine the effects of compounds 6a, 6i, and 6j on C. glabrata cells under in vivo experimental conditions.

 

Comments：

Benzimidazole-1,2,4-triazole derivatives have been synthesized and shown to have antifungal activity against four fungal strains, with three compounds (6b, 6i, and 6j) exhibiting higher antifungal activity compared to voriconazole and fluconazole, and they were suggested to be used as a new fungicidal lead targeting 14α-demethylase for further optimization and their cytotoxicity and effects on C. glabrata cells were also investigated.

Related Products

Cat.No. Product Name Information
S1331 Fluconazole Fluconazole is a fungal lanosterol 14 alpha-demethylase inhibitor, which thereby prevents the formation of ergosterol,used in the treatment and prevention of superficial and systemic fungal infections.

Related Targets

Fungal P450 (e.g. CYP17)