Synthesis, Molecular Modeling Study, and Quantum-Chemical- Based Investigations of Isoindoline-1,3-diones as Antimycobacterial Agents
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Date
2022-05-19
Journal Title
Journal ISSN
Volume Title
Publisher
American Chemical Society
Abstract
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 thinlayer
chromatography (TLC), infrared spectroscopy, 1H and 13C 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 IC50 of 18 μM, making it the most potent compound of the series.
The InhA inhibitory (IC50) 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 (1H and 13C NMR) calculations.