Integrative DFT, docking, and ADMET evaluation of a promising Schiff base inhibitor (DMBI) for tuberculosis therapy

Abstract

Tuberculosis continues to pose a serious global health threat due to the increase in drug-resistant Mycobacterium tuberculosis strains. In this study, the activity of (Z)-3-(((E)-4-(dimethylamino)benzylidene)hydrazinylidene)indolin-2-one (DMBI), a Schiff base derivative, as a potential inhibitor of tuberculosis was investigated. The molecular structure of DMBI was optimized using the B3LYP/B3PW91 methods and the 6-311G(d,p) basis set within the scope of density functional theory (DFT); the HOMO-LUMO energy gap, molecular electrostatic potential distribution, Mulliken atomic charges, and intramolecular interactions were analyzed in detail. Preliminary orbital analyses showed that the molecule exhibits significant nonlinear optical properties. Molecular docking studies with tuberculosis enzymes (PDB: 1SJ2 and 4P8N) revealed strong interactions with binding affinities of -9.7859 and -8.1283 kcal/mol, respectively. ADMET evaluations indicate that DMBI has a suitable pharmacokinetic and toxicological profile for drug development. The findings suggest that DMBI may serve as a potential anti-tuberculosis lead compound; however, further experimental and biological validation studies are required to confirm its therapeutic efficacy.

KEY WORDS: Tuberculosis, Schiff base, DFT, HOMO-LUMO, Molecular docking

Bull. Chem. Soc. Ethiop. 2027, 41(1), 99-118.                                                                                      

DOI: https://dx.doi.org/10.4314/bcse.v41i1.8