Identification of Fungicidal 2,6-Disubstituted Quinolines with Activity against Candida Biofilms

Molecules

Nicolas Delattin²  Dorothພ Bardiot¹  Arnaud Marchand¹  Patrick Chaltin¹  Katrijn De Brucker²  Bruno P. A. Cammue² 

[1] CISTIM Leuven vzw, Minderbroedersstraat 12, B-3000, Leuven, Belgium;Centre of Microbial and Plant Genetics, Katholieke Universiteit Leuven, Kasteelpark Arenberg 20, B-3001, Heverlee, Belgium

关键词: antifungal agents;    Candida spp.;    2;    6-disubstituted quinolines;    reactive oxygen species;    structure-activity relationships;   

DOI  :  10.3390/molecules171012243

来源: mdpi

【 摘 要 】

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.

【 授权许可】

CC BY   
© 2012 by the authors; licensee MDPI, Basel, Switzerland.