Influence of heterocyclic and oxime-containing farnesol analogs on quorum sensing and pathogenicity in Candida albicans

Authors

Roman Shchepin, University of Nebraska - Lincoln
Dhammika H.M.L.P. Navarathna, University of Nebraska - Lincoln
Raluca Dumitru, University of Nebraska - Lincoln
Shane Lippold, University of Nebraska - Lincoln
Kenneth W. Nickerson, University of Nebraska-LincolnFollow
Patrick Dussault, University of Nebraska-LincolnFollow

Document Type

Article

Date of this Version

1-1-2008

Comments

Published in Bioorganic & Medicinal Chemistry (2008). Copyright © 2007 Elsevier Ltd. Used by permission. http://www.sciencedirect.com/science/journal/09680896

Abstract

A series of synthetic molecules combining a geranyl backbone with a heterocyclic or oxime head group are quorum-sensing molecules that block the yeast to mycelium transition in the dimorphic fungus Candida albicans. A number of the analogs have an IC₅₀ ≤ 10 μM, a level of potency essentially identical to the natural quorum sensing signal, the sesquiterpene farnesol. Two of the most potent analogs, neither toxic toward healthy mice, display remarkably different effects when co-administered with C. albicans. While neither offers protection from candidiasis, one analog mimics farnesol in acting as a virulence factor, whereas the other has no effect. The results offer the first example of highly potent synthetic fungal quorum-sensing molecules, and provide the first evidence for the ability to decouple quorum sensing and virulence.