Design and Synthesis of Isatin‐Tagged Isoniazid Conjugates with Cogent Antituberculosis and Radical Quenching Competence: In‐vitro and In‐silico Evaluations

In pursuit of potential chemotherapeutic alternates to combat severe tuberculosis infections, novel heterocyclic templates derived from clinically approved anti‐TB drug isoniazid and isatin have been synthesized that demonstrate potent inhibitory action against Mycobacterium tuberculosis, and compound 4i with nitrophenyl motif exhibited the highest anti‐TB efficacy with a MIC value of 2.54 μM/ml. Notably, the same nitro analog 4i shows the best antioxidant efficacy among all the synthesized compounds with an IC 50 value of 37.37 μg/ml, suggesting a synergistic influence of antioxidant proficiency on the anti‐TB action. The titled compounds exhibit explicit binding affinity with the InhA receptor. The befitting biochemical reactivity and near‐appropriate pharmacokinetic proficiency of the isoniazid conjugates is reflected in the density functional theory (DFT) studies and ADMET screening. The remarkable anti‐TB action of the isoniazid cognates with marked radical quenching ability may serve as a base for developing multi‐target medications to confront drug‐resistant TB pathogens.