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.

引用

页数：7

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