Article

Projet
Protéines ABC, membranes et passage membranaire  
Ahcène BOUMENDJELBasile PERES,   
Titre
Make Azoles Active Again: Chalcones as Potent Reversal Agents of Transporters-Mediated Resistance in Candida albicans.  
Auteurs
S. Nim, P. Baghel, V.-K. Tran-Nguyen, B. Peres, K.-A. Nguyen, A. Di Pietro, P. Falson, R. Prasad, A. Boumendjel
Edition
Future Med. Chem. 2018, in press
Année
2018
Résumé
Background: Resistance against antifungals used for Candida albicans (Ca) treatment is mediated by two multidrug transporters, Mdr1p and Cdr1p, which are of enormous interest to the development of modulators combined with antifungals. Results: A set of chalcones were screened using the checkerboard liquid chemosensitization assays. Compounds 4, 10, 12 and 18, when combined with fluconazole, triggered strong sensitization on yeast strains overexpressing CaMdr1p and CaCdr1p, whereas displaying no cytotoxic by themselves towards control strains and transporter-expressing yeast cells. In the Nile Red (NR) transport assay, the two most active compounds 12 and 18 showed moderate-to-high accumulation of NR with different behaviors towards the two transporters. Conclusion: Chalcones are promising drug candidates for further development to make azole antifungals active again.