Add time:07/11/2019         Source:sciencedirect.com

A series of (2R,3S)-2-(2,4-difluorophenyl)-3-(5-{2-[4-aryl-piperazin-1-yl]-ethyl}-tetrazol-2-yl)-1-[1,2,4]-triazol-1-yl-butan-2-ol (11a–n) and (2R,3S)-2-(2,4-difluorophenyl)-3-(5-{2-[4-aryl-piperazin-1-yl]-ethyl}-tetrazole-1-yl)-1-[1,2,4]-triazol-1-yl-butan-2-ol (12a–n) has been synthesized. The antifungal activity of compounds was evaluated by in vitro agar diffusion and broth dilution assay. Compounds 11d and its positional isomer 12d having 3-trifluoromethyl substitution on the phenyl ring of piperazine demonstrated significant antifungal activity against variety of fungal cultures (Candida spp. C. neoformans and Aspergillus spp.). The compound 12d showed MIC value of 0.12 μg/mL for C. albicans, C. albicans V-01-191A-261 (resistant strain); 0.25 μg/mL for C. tropicalis, C. parapsilosis ATCC 22019 and C. krusei and MIC value of 0.5 μg/mL for C. glabrata, C. krusei ATCC 6258, which is comparable to itraconazole and better than fluconazole. Further, compound 11d showed significant activity (MIC; 0.25–0.5 μg/mL) against Candida spp. and strong anticryptococcal activity (MIC; 0.25 μg/mL) against C. neoformans.

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