Synthesis, Molecular Modeling Study, and Quantum-Chemical-Based Investigations of Isoindoline-1,3-diones as Antimycobacterial Agents

[Image: see text] The condensation of phthalic anhydride afforded structurally modified isoindoline-1,3-dione derivatives with selected amino-containing compounds. The title compounds (2–30) have been characterized by thin-layer chromatography (TLC), infrared spectroscopy, (1)H and (13)C NMR spectroscopy, and mass spectroscopy. All of the compounds were assessed for their antimycobacterial activity toward the H37Rv strain by a dual read-out assay method. Among the synthesized compounds, compound 27 possessed a significant IC(50) of 18 μM, making it the most potent compound of the series. The InhA inhibitory (IC(50)) activity of compound 27 was 8.65 μM in comparison to Triclosan (1.32 μM). Computational studies like density functional theory (DFT) study, molecular docking, and dynamic simulation studies illustrated the reactivity and stability of the synthesized compounds as InhA inhibitors. A quantum-mechanics-based DFT study was carried out to investigate the molecular and electronic properties, reactivities, and nature of bonding present in the synthesized compounds and theoretical vibrational (IR) and isotropic value ((1)H and (13)C NMR) calculations.