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Design, synthesis and antifungal activities of novel 1,2,4-triazole derivatives
- Source :
- European Journal of Medicinal Chemistry. 46:3142-3148
- Publication Year :
- 2011
- Publisher :
- Elsevier BV, 2011.
-
Abstract
- 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.
- Subjects :
- Antifungal Agents
Stereochemistry
Microbial Sensitivity Tests
Piperazines
Fungal Proteins
Sterol 14-Demethylase
Structure-Activity Relationship
chemistry.chemical_compound
Catalytic Domain
Candida albicans
Drug Discovery
medicine
Cytochrome P-450 Enzyme Inhibitors
Fluconazole
Pharmacology
Cryptococcus neoformans
Voriconazole
Fungal protein
biology
Chemistry
Lanosterol
Organic Chemistry
General Medicine
Triazoles
biology.organism_classification
Corpus albicans
Molecular Docking Simulation
Docking (molecular)
Drug Design
medicine.drug
Subjects
Details
- ISSN :
- 02235234
- Volume :
- 46
- Database :
- OpenAIRE
- Journal :
- European Journal of Medicinal Chemistry
- Accession number :
- edsair.doi.dedup.....b42ce6612aa974c7e86d9ce9c256f542