Synthesis, Antimycobacterial Activity, and Computational Insight of Novel 1,4-Benzoxazin-2-one Derivatives as Promising Candidates against Multidrug-Resistant Mycobacterium Tuberculosis

In the search for new antitubercular agents, a series of 1,4-benzoxazinone-based compounds is designed, synthesized, and evaluated. These molecules show potent antimycobacterial activity, with a minimum inhibitory concentration between 2 and 8 μg mL−1. This interesting profile includes activity against several drug-resistant strains and minimal cytotoxicity against mammalian Vero cells. Structural similarities with analogs from the literature are reinforced by molecular docking and molecular dynamics simulations, suggesting that inhibition of the menaquinone-B enzyme as a potential mechanism of action. In addition, the active compounds exhibit favorable predicted Absorption, Distribuition, Metabolism, and Excretion (ADME) properties, indicating their potential for oral administration in humans.