Abstract
In order to meet the urgent need for novel antifungal agents with improved activity and broader spectrum, a series of 1-(1H-1,2,4-triazol-1-yl)-2-(2,4-difluorophenyl)-3-[(4-substituted trifluoromethyl phenyl)-piperazin-1-yl]-propan-2-ols were designed, synthesized and evaluated as antifungal agents. The MIC(80) values indicate that the compounds 7a-7q, 8a-8d showed higher antifungal activities against Candida albicans than 5a-5i, 6a-6j. Moreover, the molecular model for the binding between compound 5a, 7a and the active site of CACYP51 was provided based on the computational docking results, and the structure-activity relationship was analyzed.
Copyright © 2011 Elsevier Masson SAS. All rights reserved.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Antifungal Agents / chemical synthesis*
-
Antifungal Agents / pharmacology
-
Aspergillus fumigatus / drug effects
-
Aspergillus fumigatus / growth & development
-
Candida albicans / drug effects
-
Candida albicans / growth & development
-
Catalytic Domain
-
Cryptococcus neoformans / drug effects
-
Cryptococcus neoformans / growth & development
-
Cytochrome P-450 Enzyme Inhibitors / chemical synthesis*
-
Cytochrome P-450 Enzyme Inhibitors / pharmacology
-
Drug Design
-
Fluconazole / pharmacology
-
Fungal Proteins / antagonists & inhibitors*
-
Fungal Proteins / chemistry
-
Microbial Sensitivity Tests
-
Molecular Docking Simulation
-
Piperazines / chemistry
-
Propanols / chemistry
-
Sterol 14-Demethylase / chemistry*
-
Structure-Activity Relationship
-
Triazoles / chemical synthesis*
-
Triazoles / pharmacology
-
Voriconazole / pharmacology
Substances
-
Antifungal Agents
-
Cytochrome P-450 Enzyme Inhibitors
-
Fungal Proteins
-
Piperazines
-
Propanols
-
Triazoles
-
Fluconazole
-
Sterol 14-Demethylase
-
Voriconazole