Synthesis and antifungal activities of new fluconazole analogues with azaheterocycle moiety

Nicolas Lebouvier; Fabrice Pagniez; Muriel Duflos; Patrice Le Pape; Young Min Na; Guillaume Le Baut; Marc Le Borgne

doi:10.1016/j.bmcl.2007.04.038

Synthesis and antifungal activities of new fluconazole analogues with azaheterocycle moiety

Bioorg Med Chem Lett. 2007 Jul 1;17(13):3686-9. doi: 10.1016/j.bmcl.2007.04.038. Epub 2007 Apr 19.

Authors

Nicolas Lebouvier¹, Fabrice Pagniez, Muriel Duflos, Patrice Le Pape, Young Min Na, Guillaume Le Baut, Marc Le Borgne

Affiliation

¹ Nantes University, Nantes Atlantique Universities, Pharmacochemistry Department, BioCiT UPRES EA 1155, Faculty of Pharmacy, Nantes, France.

PMID: 17482460
DOI: 10.1016/j.bmcl.2007.04.038

Abstract

A series of fluconazole analogues 5-20 incorporating azaindole and indole moieties were prepared using oxirane intermediates synthesized under microwave irradiation. All of the compounds were evaluated in vitro against two clinically important fungi, Candida albicans and Aspergillus fumigatus. Four derivatives 6, 13, 14 and 18 exerted high antifungal activity against C. albicans with MIC(80) values 3- to 28-fold lower than that of fluconazole.

MeSH terms

Antifungal Agents / chemical synthesis*
Antifungal Agents / chemistry*
Aspergillus fumigatus / metabolism
Candida albicans / metabolism
Chemistry, Pharmaceutical / methods*
Drug Design
Drug Resistance, Fungal
Fluconazole / chemical synthesis*
Fluconazole / chemistry*
Humans
Inhibitory Concentration 50
Microbial Sensitivity Tests*
Models, Chemical
Time Factors
Triazoles / chemistry

Substances

Antifungal Agents
Triazoles
Fluconazole