Identification of benzothiazones containing a hexahydropyrrolo[3,4-c]pyrrol moiety as antitubercular agents against MDR-MTB

Abstract

IMB1603, a spiro-benzothiazone compound discovered by our lab, displayed potent anti-MTB activity in vitro and in vivo. In this study, we reported a series of new BTZs containing the hexahydropyrrolo[3,4-c]pyrrol moiety based on the structure of IMB1603. Among them, BTZs 11 and 24 displayed potent anti-MTB (MIC < 0.035 μM) and MDR-MTB (MIC, 0.053–0.102 μM) activity, good solubility (1.82–1.85 μg mL⁻¹), and low cytotoxicity (CC₅₀ > 200 μM), suggesting BTZs 11 and 24 may serve as promising candidates for further study. The molecular docking study of 11 toward DprE was also investigated, and revealed that 11 mimicked the binding pattern of PBTZ169 in the active site of DprE1.