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

Molecules. 2012 Oct 18;17(10):12243-51. doi: 10.3390/molecules171012243.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antifungal Agents / chemistry*
  • Antifungal Agents / pharmacology*
  • Biofilms / drug effects*
  • Candida / drug effects*
  • Candida / metabolism
  • Microbial Sensitivity Tests
  • Quinolines / chemistry*
  • Quinolines / pharmacology*
  • Reactive Oxygen Species / metabolism

Substances

  • Antifungal Agents
  • Quinolines
  • Reactive Oxygen Species