Synthesis, DFT study, in silico ADMET evaluation, molecular docking, and QSAR analysis of new anti-tuberculosis drugs derived from 2-hydroxybenzohydrazide derivatives.

Abstract

This study investigates the potential of novel thiazole and hydroxybenzohydrazide derivatives as antitubercular agents. Using molecular docking and density functional theory (DFT) calculations, the binding affinities of these derivatives to the enoyl-acyl carrier protein reductase (InhA) enzyme of M. tb were assessed. InhA is crucial for the mycobacterial fatty acid synthase II (FAS-II) pathway, making it a prime target for drug development. QSAR analysis was employed to relate molecular descriptors to biological activity, and ADMET descriptors evaluated the pharmacokinetics and toxicity of the compounds. Experimental synthesis of the compounds and their characterization via IR and NMR spectroscopy confirmed their structures. DFT calculations revealed multiple conformers for each compound, with specific isomers showing enhanced stability and favorable binding interactions with InhA. These findings suggest that the synthesized derivatives have potential as new antitubercular agents, offering a basis for future drug development strategies against multidrug-resistant TB.