Antitubercular agent-32

Antitubercular agent-32 is a derivate of Benzothiazinone (HY-13579A), inhibits M. tuberculosis, and shows improved metabolic stability and enhanced water solubility. Antitubercular agent-32 exerts antitubercular effect by targeting decaprenylphosphoryl-β-D-ribose 2’-oxidase (DprE1, IC50=3.9 μM)[1].

Research Areas >> Infection

Signaling Pathways >> Anti-infection >> Bacterial

Antitubercular agent-32 (compound 8) (0-7.5 mg/mL; 48 h) shows low cytotoxicity and inhibits M. tuberculosis H37Rv with the minimum inhibition concentration (MIC) of 40 nM[1]. Antitubercular agent-32 (0-20 μM) inhibits decaprenylphosphoryl-β-D-ribose 2’-oxidase (DprE1, 0.5 μM), an enzyme essential for the biosynthesis of mycobacterial cell wall, with an IC50 value of 3.9 μM[1]. Antitubercular agent-32 (1 μM; 10 min) exhibits metabolic stability in the liver microsomal metabolic of both human (HLM) and mouse (MLM), with fast clearance rates of 77 mL/min/kg (HLM) and 163 mL/min/kg (MLM), respectively[1]. Cell Cytotoxicity Assay[1] Cell Line: HepG2 cells Concentration: 0, 15, 30, 75, 150, 300, 750, 1500, 3000, and 7500 ng/mL Incubation Time: 48 hours Result: There were no significantly growth inhibitions of HepG2 cells.

[1]. Shi R, et al. Development of 6-Methanesulfonyl-8-nitrobenzothiazinone Based Antitubercular Agents. ACS Med Chem Lett. 2022 Mar 10;13(4):593-598.