Blocking and dislocation of Candida albicans Cdr1p transporter by styrylquinolines

Abstract Styrylquinolines are a novel group of quinoline drugs that are known to have p53-independent antiproliferative activity and antiviral properties. This study evaluated the antifungal activity of these drugs more deeply, particularly their activity modulation towards Cdr1p, the main multidrug transporter of Candida albicans . Styrylquinolines were found to have antifungal activity and to work synergistically with fluconazole. Additionally, they decreased the extracellular concentration of rhodamine 6G in ABC-transporter-expressing cells. The cellular localization of GFP-tagged Cdr1p was assessed by epifluorescent microscopy. Styrylquinolines induce expression of Cdr1p, as confirmed by Western blotting. Three of four drugs tested caused the partial delocalization of transport protein to the cytoplasm. These results show the first evidence that styrylquinolines decrease the activity of ABC multidrug transporters in C. albicans .