Development of Narrow-Spectrum Topoisomerase-Targeting Antibacterials against Mycobacteria

The study presents the discovery of new 2-pyrrolamidobenzothiazole-based inhibitors targeting mycobacterial DNA gyrase. Among the synthesized compounds, 49 and 51 exhibit excellent antibacterial activity specifically against Mycobacterium tuberculosis and Mycobacterium abscessus. These compounds are capable of penetrating infected macrophages and significantly reducing the intracellular bacterial load. Compound 51, in particular, is highlighted as a potent inhibitor of DNA gyrase, demonstrating low nanomolar inhibitory activity.