Discovery of novel anti-tuberculosis agents with pyrrolo[1,2-a]quinoxaline-based scaffold.
Wang T, Tang Y, Yang Y, An Q, Sang Z, Yang T, Liu P, Zhang T, Deng Y, Luo Y.
A series of small molecules with novel pyrrolo[1,2-a]quinoxaline-based scaffold was designed via molecular hybridization of privileged agents active against Mycobacterium tuberculosis. Twenty-three compounds were synthesized and investigated for their antitubercular activities in vitro where ten compounds showed appreciable activities and moderate cytotoxicity. Compound 12g with MIC values of 5 μg/ml as a representative may possess better oral bioavailability and indicated high permeability by the parallel artificial membrane permeation assay of the blood-brain barrier (PAMPA-BBB). Further, the determination of enzyme inhibition and molecular docking study indicated that InhA may be the biological target of the active compounds. The results suggest the pyrrolo[1,2-a]quinoxaline hybrids as potential antitubercular leads for the development of new antitubercular agents.