Optimization of N-benzyl-5-nitrofuran-2-carboxamide as an antitubercular agent.

ABSTRACT: The optimization campaign for a nitrofuran antitubercular hit (N-benzyl-5-nitrofuran-2-carboxamide; JSF-3449) led to the design, synthesis, and biological profiling of a family of analogs. These compounds exhibited potent in vitro antitubercular activity (MIC?=?0.019-0.20??M) against the Mycobacterium tuberculosis H37Rv strain and low in vitro cytotoxicity (CC50?=?40->120??M) towards Vero cells. Significant improvements in mouse liver microsomal stability and mouse pharmacokinetic profile were realized by introduction of an ?, ?-dimethylbenzyl moiety. Among these compounds, JSF-4088 is highlighted due to its in vitro antitubercular potency (MIC?=?0.019??M) and Vero cell cytotoxicity (CC50?>?120??M). The findings suggest a rationale for the continued evolution of this promising series of antitubercular small molecules.

SUBMITTER: Gallardo-Macias R 

PROVIDER: S-EPMC6368976 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature