Identification of fungicidal 2,6-disubstituted quinolines with activity against Candida biofilms

We have identified two subseries of 2,6-disubstituted quinolines, consisting of 6-amide and 6-urea derivatives, which are characterized by fungicidal activity against Candida albicans with minimal fungicidal concentration (MFC) values < 15 µM. The 6-amide derivatives displayed the highest fungicidal activity against C. albicans, in particular compounds 1, 5 and 6 characterized by MFC values of 6.25-12.5 µM. Compounds 1 and 5 of this series displayed fungicidal activity against the emerging pathogen Candida glabrata (MFC < 50 µM). The 6-amide derivatives 1, 2, 5, and 6 and the 6-urea derivatives 10, 12, 13 and 15 could also eradicate C. albicans biofilms. We found that the 6-urea derivatives 10, 13, and 15 induced accumulation of endogenous reactive oxygen species in Candida albicans biofilms.