Synthesis and Antichlamydial Activity of Molecules Based on Dysregulators of Cylindrical Proteases

Chlamydia trachomatis is the most common sexually
transmitted bacterial disease globally and the leading cause of infertility
and preventable infectious blindness (trachoma) in the world. Unfortunately,
there is no FDA-approved treatment specific for chlamydial infections.
We recently reported two sulfonylpyridines that halt the growth of
the pathogen. Herein, we present a SAR of the sulfonylpyridine molecule
by introducing substituents on the aromatic regions. Biological evaluation
studies showed that several analogues can impair the growth of C. trachomatis without affecting host cell viability. The
compounds did not kill other bacteria, indicating selectivity for
Chlamydia. The compounds presented mild toxicity
toward mammalian cell lines. The compounds were found to be nonmutagenic
in a Drosophila melanogaster assay and exhibited
a promising stability in both plasma and gastric fluid. The presented
results indicate this scaffold is a promising starting point for the
development of selective antichlamydial drugs.