Make azoles active again: chalcones as potent reversal agents of transporters-mediated resistance in Candida albicans. (25th July 2018)

• Record Type: Journal Article
• Authors: Nim, Shweta; Baghel, Pratima; Tran-Nguyen, Viet-Khoa; Peres, Basile; Nguyen, Kim-Anh; Pietro, Attilio Di; Falson, Pierre; Prasad, Rajendra; Boumendjel, Ahcène
• Is Part Of: Future medicinal chemistry. Volume 10:Number 18(2018)
• Page Start: 2177
• Page End: 2186
• Publication Date: 2018-07-25
• Subjects: antifungal -- Candida albicans -- Cdr1p -- chalcones -- Mdr1p -- resistance; Pharmaceutical chemistry -- Periodicals; 615.19005
• DOI: 10.4155/fmc-2018-0081
• Languages: English
• ISSNs: 1756-8919

Abstract

Aim: 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.Experimental: A set of chalcones was synthesized by condensation reactions in laboratory and was then subject to biological assays to evaluate the effects on different yeast strains. Results: The obtained chalcones were screened using the checkerboard liquid chemosensitization assays. Compounds4, 10, 12 and18, when combined with fluconazole, triggered strong sensitization on yeast strains overexpressing Ca Mdr1p and Ca Cdr1p, whereas displaying no cytotoxicity by themselves towards control strains and transporter-expressing yeast cells. In the Nile Red transport assay, the two most active compounds, 12 and18 showed moderate-to-high accumulation of Nile Red with different behaviors towards the two transporters.Conclusion: Chalcones are promising drug candidates for further development to make azole antifungals active again. Graphical abstract: