Design, synthesis and antifungal activities of novel 1,2,4-triazole derivatives.
A series of novel 1,2,4-triazole derivatives with a 4-(4-substitutedphenyl) piperazine side chain were designed and synthesized based on the structure of lanosterol 14α-demethylase (CYP51). Their antifungal activities against eight human pathogenic fungi were evaluated in vitro by measuring the minimal inhibitory concentrations. Nearly all tested compounds were found to be ... more potent against Candida albicans than control drug fluconazole. Noticeably, the MIC(80) value of compounds 6,7,9,14 and 29 is 16 times lower than that of voriconazole against C. albicans. The activities of compounds 7 and 21 against Cryptococcus neoformans in vitro are comparable to that of voriconazole with a MIC(80) value of 0.0156 μg/mL. Moreover, the molecular model for the binding between compound 7 and the active site of CACYP51 was provided based on the computational docking results.
Mesh Terms:
Antifungal Agents, Azoles, Binding Sites, Catalytic Domain, Computer Simulation, Cytochrome P-450 Enzyme System, Drug Design, Microbial Sensitivity Tests, Oximes, Sterol 14-Demethylase, Structure-Activity Relationship
Antifungal Agents, Azoles, Binding Sites, Catalytic Domain, Computer Simulation, Cytochrome P-450 Enzyme System, Drug Design, Microbial Sensitivity Tests, Oximes, Sterol 14-Demethylase, Structure-Activity Relationship
Eur J Med Chem
Date: Jul. 01, 2011
PubMed ID: 21420761
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