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

Roman Shchepin, Dhammika H.M.L.P. Navarathna, Raluca Dumitru, Shane Lippold, Kenneth Nickerson, Patrick H Dussault

Research output: Contribution to journalArticle

9 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)1842-1848
Number of pages7
JournalBioorganic and Medicinal Chemistry
Volume16
Issue number4
DOIs
StatePublished - Feb 15 2008

Fingerprint

Farnesol
Quorum Sensing
Oximes
Candida
Candida albicans
Virulence
Molecules
Sesquiterpenes
Poisons
Virulence Factors
Fungi
Yeast
Candidiasis
Mycelium
Inhibitory Concentration 50
Yeasts

Keywords

  • Candida albicans
  • Candidiasis
  • Farnesol
  • Oxime
  • Quorum sensing
  • Tetrazole
  • Thioimidazole
  • Thiotetrazole
  • Thiotriazole
  • Triazole
  • Virulence

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry

Cite this

Influence of heterocyclic and oxime-containing farnesol analogs on quorum sensing and pathogenicity in Candida albicans. / Shchepin, Roman; Navarathna, Dhammika H.M.L.P.; Dumitru, Raluca; Lippold, Shane; Nickerson, Kenneth; Dussault, Patrick H.

In: Bioorganic and Medicinal Chemistry, Vol. 16, No. 4, 15.02.2008, p. 1842-1848.

Research output: Contribution to journalArticle

Shchepin, Roman ; Navarathna, Dhammika H.M.L.P. ; Dumitru, Raluca ; Lippold, Shane ; Nickerson, Kenneth ; Dussault, Patrick H. / Influence of heterocyclic and oxime-containing farnesol analogs on quorum sensing and pathogenicity in Candida albicans. In: Bioorganic and Medicinal Chemistry. 2008 ; Vol. 16, No. 4. pp. 1842-1848.
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