Future medicinal chemistry · 2018
Make azoles active again: chalcones as potent reversal agents of transporters-mediated resistance in Candida albicans.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод пока не подготовлен
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Nim Shweta, Baghel Pratima, Tran-Nguyen Viet-Khoa, Peres Basile, Nguyen Kim-Anh, Pietro Attilio Di, Falson Pierre, Prasad Rajendra, Boumendjel Ahcène
Аннотация
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. Compounds 4, 10, 12 and 18, when combined with fluconazole, triggered strong sensitization on yeast strains overexpressing CaMdr1p and CaCdr1p, 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 and 18 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.
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. Compounds 4, 10, 12 and 18, when combined with fluconazole, triggered strong sensitization on yeast strains overexpressing CaMdr1p and CaCdr1p, 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 and 18 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.