Shchepin Roman, Navarathna Dhammika H M L P, Dumitru Raluca, Lippold Shane, Nickerson Kenneth W, Dussault Patrick H
Department of Chemistry, University of Nebraska-Lincoln, Lincoln, NE 68588, USA.
Bioorg Med Chem. 2008 Feb 15;16(4):1842-8. doi: 10.1016/j.bmc.2007.11.011. Epub 2007 Nov 6.
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 microM, 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.
一系列将香叶基主链与杂环或肟头基结合的合成分子是群体感应分子，它们可阻断二态真菌白色念珠菌从酵母形态向菌丝形态的转变。许多类似物的半数抑制浓度（IC50）为10微摩尔，其效力水平与天然群体感应信号倍半萜法尼醇基本相同。两种最有效的类似物对健康小鼠均无毒，与白色念珠菌共同给药时显示出明显不同的效果。虽然两者都不能预防念珠菌病，但一种类似物在作为毒力因子方面模仿法尼醇，而另一种则没有效果。这些结果提供了高效合成真菌群体感应分子的首个实例，并为将群体感应与毒力解耦的能力提供了首个证据。
