A series of 1-(1H-1,2,4-triazol-1-yl)-2-(2,4-difluorophenyl)-3-[(4-substitutedphenyl)-piperazin-1-yl]-propan-2-ols were designed and synthesized on the basis of the active site of fungal Lanosterol 14α-demethylase(CY...A series of 1-(1H-1,2,4-triazol-1-yl)-2-(2,4-difluorophenyl)-3-[(4-substitutedphenyl)-piperazin-1-yl]-propan-2-ols were designed and synthesized on the basis of the active site of fungal Lanosterol 14α-demethylase(CYP51),the structure-activity relationships and antimycotic mechanism of azole antifungal agents.Their structures were confirmed via elemental analysis,IR,MS and 1H NMR.The results of preliminary antifungal tests against eight human pathogenic fungi(Candida albicans,Candida parapsilosis,Candida tropicalis,Cryptococcus neoformans,Aspergillus fumigatus,Trichophyton rubrum,Fonsecaea compacta,Microsporum gypseum)in vitro show that all compounds exhibited higher activities against fungi than that of fluconazole,voriconazole and amphotericin B;compounds 4a,4b and 4d showed higher activities against Aspergillus fumigatus than fluconazole and voriconazole(with the MIC values of 0.25,0.25 and 0.25 μg/mL respectively).For antifungal activity of these novel triazole derivatives,it is very helpful to introduce the 4-(4-substitutedphenyl)piperazine as side chains to interact with the residues of the narrow hydrophobic cleft of CYP51 and adjust the physico-chemical properties of title molecules.展开更多
文摘A series of 1-(1H-1,2,4-triazol-1-yl)-2-(2,4-difluorophenyl)-3-[(4-substitutedphenyl)-piperazin-1-yl]-propan-2-ols were designed and synthesized on the basis of the active site of fungal Lanosterol 14α-demethylase(CYP51),the structure-activity relationships and antimycotic mechanism of azole antifungal agents.Their structures were confirmed via elemental analysis,IR,MS and 1H NMR.The results of preliminary antifungal tests against eight human pathogenic fungi(Candida albicans,Candida parapsilosis,Candida tropicalis,Cryptococcus neoformans,Aspergillus fumigatus,Trichophyton rubrum,Fonsecaea compacta,Microsporum gypseum)in vitro show that all compounds exhibited higher activities against fungi than that of fluconazole,voriconazole and amphotericin B;compounds 4a,4b and 4d showed higher activities against Aspergillus fumigatus than fluconazole and voriconazole(with the MIC values of 0.25,0.25 and 0.25 μg/mL respectively).For antifungal activity of these novel triazole derivatives,it is very helpful to introduce the 4-(4-substitutedphenyl)piperazine as side chains to interact with the residues of the narrow hydrophobic cleft of CYP51 and adjust the physico-chemical properties of title molecules.
