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

被引：1
|
作者：
Yang, Baiyuan [1 ]
Sukheja, Paridhi [1 ]
Qin, Bo [1 ]
Li, Gencheng [2 ]
Bare, Grant A. L. [2 ]
Cascioferro, Alessandro [1 ]
Love, Melissa S. [1 ]
Petrassi, H. Michael [1 ]
Sharpless, K. Barry [2 ]
Mcnamara, Case W. [1 ]
Chatterjee, Arnab K. [1 ]
机构：
[1] Calibr, Div Scripps Res, La Jolla, CA 92037 USA
[2] Scripps Res, Dept Chem, La Jolla, CA 92037 USA
来源：
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2024年 / 98卷
基金：
比尔及梅琳达.盖茨基金会;
关键词：
Mycobacterium tuberculosis; Aryl fluorosulfate; Sulfur (VI) fluoride exchange; Structure -activity relationship studies; Anti-TB activity; Pharmacokinetic; SuFEx;
D O I：
10.1016/j.bmcl.2023.129596
中图分类号：
R914 [药物化学];
学科分类号：
100701 ;
摘要：
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 mu M 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.
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页数：7
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