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.


CONCLUSIONS
The structure-activity relationship presented here defines an important step toward the molecular target of this compound class, which is still elusive.
Institute of Chemistry, Humboldt-Universität zu Berlin, Brook-Taylor-Str. 2, 12489 Berlin.|Chemistry Department, Faculty of Science, Suez Canal University, Ismailia, Egypt.
Essa M
EM
Saied
Junior Research Group 'Sexually Transmitted Bacterial Pathogens' (NG 5), Robert Koch Institute, Berlin, Germany.
Sebastian
S
Banhart
Junior Research Group 'Sexually Transmitted Bacterial Pathogens' (NG 5), Robert Koch Institute, Berlin, Germany.
Sophie E
SE
Bürkle
Junior Research Group 'Sexually Transmitted Bacterial Pathogens' (NG 5), Robert Koch Institute, Berlin, Germany.
Dagmar
D
Heuer
Institute of Chemistry, Humboldt-Universität zu Berlin, Brook-Taylor-Str. 2, 12489 Berlin.
Christoph
C
Arenz
D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D002518:Ceramides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D002692:Chlamydia trachomatis / Q000187:drug effects* / Q000254:growth & development*; D004305:Dose-Response Relationship, Drug; D006367:HeLa Cells; D006801:Humans; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
D000900:Anti-Bacterial Agents; D002518:Ceramides