A series of ceramide analogs modified at the 1-position with potent activity against the intracellular growth of Chlamydia trachomatis

Background: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. Results: 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. Conclusion: The structure-activity relationship presented here defines an important step toward the molecular target of this compound class, which is still elusive.