Synthesis and evaluation of novel 1-(1H-1,2,4-triazol-1-yl)-2-(2,4-difluorophenyl)-3-[(4-substitutedphenyl)-piperazin-1-yl]-propan-2-ols as antifungal agents

Abstract: A series of 1-(1H-1,2,4-triazol-1-yl)-2-(2,4-difluorophenyl)-3-[(4-substitutedphenyl)-piperazin-1-yl]-propan-2-ols have been designed and synthesized on the basis of the structure–activity relationships and antimycotic mechanism of azole antifungal agents. Their structures were confirmed by elemental analysis, IR, MS, 1H NMR and 13C NMR. Results of preliminary antifungal tests against six human pathogenic fungi (Candida albicans, Candida parapsilosis, Cryptococcus neoformans, Candida tropicalis, inherently fluconazole-resistant Candida krusei, Candida glabrata) in vitro showed that all title compounds exhibited activity against fungi tested to some extent except against C. tropicalis. Compound 5b showed higher activity against C. albicans, C. parapsilosis and C. krusei than fluconazole, and its MIC values were determined to be 0.5μg/mL, 1μg/mL and 4μg/mL, respectively. Compound 5k showed higher activities against Torulopsis glabrata than fluconazole (with the MIC value of 2μg/mL). Compounds 5a, 5c, 5f, 5g, 5i exhibited higher activities against C. parapsilosis than fluconazole (with the MIC values of 2μg/mL, 2μg/mL, 2μg/mL, 1μg/mL and 2μg/mL, respectively). [Copyright &y& Elsevier]