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

CHHONKER, YASHPAL SINGH; BLOCKER, AMANDA M.; LEAL, EMILSE S.; MONGE, MARÍA EUGENIA; RODRIGUES DE ALMEIDA, NATHALIA; GUTERRES, ZAIRA DA ROSA; FISHER, DEREK J.; BOLLINI, MARIELA; CONDA-SHERIDAN, MARTIN; SELEEM, MOHAMED A.; MURRY, DARYL J.; KUWABARA, SHIOMI; MARTINEFSKI, MANUELA R.; OUELLETTE, SCOT P.

JOURNAL OF MEDICINAL CHEMISTRY

AMER CHEMICAL SOC

Lugar: Washington; Año: 2020 vol. 63 p. 4370 - 4387

0022-2623

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 aSAR 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 presnted mild toxicity towards mammaliancell lines. The compounds were found to be non-mutagenic 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 anti-chlamydial drugs.