Synthesis and structure-activity relationships of aryl fluorosulfate-based inhibitors as novel antitubercular agents.

Bioorganic & medicinal chemistry letters, Volume: 98
January 15, 2024
Baiyuan Yang B, Paridhi Sukheja P, Bo Qin B, Gencheng Li G, Grant A L Bare GAL, Alessandro Cascioferro A, Melissa S Love MS, H Michael Petrassi HM, K Barry Sharpless KB, Case W McNamara CW, Arnab K Chatterjee AK

To identify new compounds that can effectively inhibit Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis (TB), we screened, synthesized, and evaluated a series of novel aryl fluorosulfate derivatives for their in vitro inhibitory activity against Mtb. Compound 21b exhibited an in vitro minimum inhibitory concentration (MIC) of 0.06 µM against Mtb, no cytotoxicity against both HEK293T and HepG2 mammalian cell lines, and had good in vivo mouse plasma exposure and lung concentration with a 20 mg/kg oral dose, which supports advanced development as a new chemical entity for TB treatment.

Courtesy of the U.S. National Library of Medicine