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 language | English (US) |
|---|---|
| Pages (from-to) | 1842-1848 |
| Number of pages | 7 |
| Journal | Bioorganic and Medicinal Chemistry |
| Volume | 16 |
| Issue number | 4 |
| DOIs | |
| State | Published - Feb 15 2008 |
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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 journal › Article
}
TY - JOUR
T1 - Influence of heterocyclic and oxime-containing farnesol analogs on quorum sensing and pathogenicity in Candida albicans
AU - Shchepin, Roman
AU - Navarathna, Dhammika H.M.L.P.
AU - Dumitru, Raluca
AU - Lippold, Shane
AU - Nickerson, Kenneth
AU - Dussault, Patrick H
PY - 2008/2/15
Y1 - 2008/2/15
N2 - 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.
AB - 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.
KW - Candida albicans
KW - Candidiasis
KW - Farnesol
KW - Oxime
KW - Quorum sensing
KW - Tetrazole
KW - Thioimidazole
KW - Thiotetrazole
KW - Thiotriazole
KW - Triazole
KW - Virulence
UR - http://www.scopus.com/inward/record.url?scp=38949177754&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=38949177754&partnerID=8YFLogxK
U2 - 10.1016/j.bmc.2007.11.011
DO - 10.1016/j.bmc.2007.11.011
M3 - Article
VL - 16
SP - 1842
EP - 1848
JO - Bioorganic and Medicinal Chemistry
JF - Bioorganic and Medicinal Chemistry
SN - 0968-0896
IS - 4
ER -