Saied Essa M, Banhart Sebastian, Bürkle Sophie E, Heuer Dagmar, Arenz Christoph
Institute of Chemistry, Humboldt-Universität zu Berlin, Brook-Taylor-Str. 2, 12489 Berlin.
Chemistry Department, Faculty of Science, Suez Canal University, Ismailia, Egypt.
Future Med Chem. 2015;7(15):1971-80. doi: 10.4155/fmc.15.126. Epub 2015 Oct 23.
Chlamydia trachomatis is an intracellular pathogen that requires different nutrients, including sphingolipids, for survival. Components for the transport and biosynthesis of sphingolipids thus may have a potential as antichlamydial targets.
In this study, we synthesized a collection of 24 ceramide derivatives. Three derivatives show pronounced activity with submicromolar IC50. The potency of these compounds was one order of magnitude higher than that of the antibiotic chloramphenicol. We show a detailed structure-activity relationship study for this novel compound class exhibiting a significant effect on the growth of C. trachomatis L2 without penetrating the bacteria itself.
The structure-activity relationship presented here defines an important step toward the molecular target of this compound class, which is still elusive.
沙眼衣原体是一种细胞内病原体，需要包括鞘脂在内的不同营养物质才能存活。因此，鞘脂转运和生物合成的成分可能具有作为抗衣原体靶点的潜力。
在本研究中，我们合成了24种神经酰胺衍生物。三种衍生物表现出显著活性，IC50为亚微摩尔级。这些化合物的效力比抗生素氯霉素高一个数量级。我们对这一类新型化合物进行了详细的构效关系研究，结果表明其对沙眼衣原体L2的生长有显著影响，且不会穿透细菌本身。
本文提出的构效关系为这一类化合物的分子靶点研究迈出了重要一步，该靶点仍不明确。
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