Synthesis and biological evaluation of sulfonylpyridine derivatives as potential anti-chlamydia agents.
Bioorg Med Chem
; 91: 117401, 2023 08 15.
Article
in En
| MEDLINE
| ID: mdl-37453189
ABSTRACT
Chlamydia trachomatis is the most prevalent sexually transmitted bacterial infection in the United States and the world. This pathogen can cause health problems ranging from trachoma (blindness) to damage of the fallopian tubes or ectopic pregnancy, which can be life-threatening if not treated properly. To this day, there is no chlamydia-specific drug on the market. Previously, we reported the activity and basic structure-activity relationships (SAR) of sulfonylpyridine molecules that possess antichlamydial action. Based on those results, we prepared a new series of derivatives. Our data indicate the new analogs can halt the growth of C. trachomatis. The lead compound, 22, was more active than our previous molecules and did not affect the growth of S. aureus and E. coli, suggesting bacterial selectivity. We performed docking studies on the presumed target, the cylindrical protease of Chlamydia. The in-silico studies partially explained the in vitro biological result as well as predicted a possible binding pose in the binding pocket. The top compound displayed a good cytotoxicity profile towards mammalian cell lines and was stable in both serum and stimulated gastric fluid. The presented data suggests the sulfonylpyridines are promising and selective anti-chlamydial compounds that merit further structural optimization.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Chlamydia Infections
Limits:
Animals
/
Female
/
Humans
Language:
En
Journal:
Bioorg Med Chem
Journal subject:
BIOQUIMICA
/
QUIMICA
Year:
2023
Document type:
Article
Affiliation country:
United States