Antitubercular agent-56, a derivative of Questiomycin A, is a potent antitubercular compound effective when taken orally. By inhibiting FabD (Kd = 9.39 μM; IC50 = 49.60 μM), it compromises the cell membrane integrity of Mycobacterium tuberculosis. Antitubercular agent-56 demonstrates significant intracellular antimycobacterial activity against Mycobacterium tuberculosis (MTB) and drug-resistant MTB both in vitro and in vivo, making it valuable for tuberculosis (TB) research.

FabD:9.39 μM (Kd)

Antitubercular agent-56 (compound B10) exhibits potent antitubercular activity against Mycobacterium tuberculosis H37Rv with a minimum inhibitory concentration (MIC) of 0.15 μg/mL and shows efficacy against both drug-sensitive and drug-resistant strains with an MIC range of 0.063 to 0.25 μg/mL. It demonstrates low cytotoxicity in Vero, HepG2, and J774A.1 cells with IC50 values of >128, >80, and >80 μg/mL, respectively. Additionally, Antitubercular agent-56 shows strong bactericidal activity against the H37Rv strain and clinical isolates in a concentration- and time-dependent manner (1/2 × MIC-16 × MIC; 0-14 days). The compound effectively penetrates macrophages and inhibits the growth of intracellular Mycobacterium tuberculosis (MTB) at concentrations of 1-4 μg/mL over 72 hours. Furthermore, at 4 × MIC for 30 minutes, it significantly enhances mycobacterial membrane permeability, indicating its disruptive effect on cell wall integrity.

Antitubercular agent-56, known as compound B10, administered at 100 mg/kg through oral gavage five times weekly for three weeks, effectively reduces the bacterial load in the lungs of mice infected with Mycobacterium tuberculosis. Additionally, a single oral gavage dose of 500 mg/kg in mice demonstrates a favorable safety profile.