Quorum Sensing in Candida Albicans: Probing Farnesol's Mode of Action With 40 Natural and Synthetic Farnesol Analogs

Chem Biol. 2003 Aug;10(8):743-50. doi: 10.1016/s1074-5521(03)00158-3.

Abstract

The dimorphic fungus Candida albicans produces extracellular farnesol (3,7,11-trimethyl-2,6,10-dodecatriene-1-ol) which acts as a quorum-sensing molecule (QSM) to suppress filamentation. Of four possible geometric isomers of farnesol, only the E,E isomer possesses QSM activity. We tested 40 natural and synthetic analogs of farnesol for their activity in an N-acetylglucosamine-induced differentiation assay for germ tube formation (GTF). Modified structural features include the head group, chain length, presence or absence of the three double bonds, substitution of a backbone carbon by S, O, N, and Se heteroatoms, presence or absence of a 3-methyl branch, and the bulkiness of the hydrophobic tail. Of the 40 compounds, 22 showed QSM activity by their ability to reduce GTF by 50%. However, even the most active of the analogs tested had only 7.3% of the activity of E,E-farnesol. Structure-activity relationships were examined in terms of the likely presence in C. albicans of a farnesol binding receptor protein.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Antifungal Agents / chemistry
  • Antifungal Agents / pharmacology*
  • Candida albicans / drug effects*
  • Candida albicans / growth & development
  • Candida albicans / metabolism
  • Farnesol / analogs & derivatives*
  • Farnesol / pharmacology*
  • Inhibitory Concentration 50
  • Molecular Structure

Substances

  • Antifungal Agents
  • Farnesol