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.
Centre of Microbial and Plant Genetics, Katholieke Universiteit Leuven, Kasteelpark Arenberg 20, B-3001, Heverlee, Belgium.
Nicolas
N
Delattin
Dorothée
D
Bardiot
Arnaud
A
Marchand
Patrick
P
Chaltin
Katrijn
K
De Brucker
Bruno P A
BP
Cammue
Karin
K
Thevissen
D000935:Antifungal Agents / Q000737:chemistry* / Q000494:pharmacology*; D018441:Biofilms / Q000187:drug effects*; D002175:Candida / Q000187:drug effects* / Q000378:metabolism; D008826:Microbial Sensitivity Tests; D011804:Quinolines / Q000737:chemistry* / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism
D000935:Antifungal Agents; D011804:Quinolines; D017382:Reactive Oxygen Species