Evaluation of anti-tuberculosis activity of some oxotitanium(IV) Schiff base complexes; molecular docking, dynamics simulation and ADMET studies

Abstract

Schiff base and their metal complexes have a wide range of chemical, biological, and medicinal applications including tuberculosis. Multi-drug resistant and extensively drug-resistant tuberculosis indicating the importance of new potent agent for tuberculosis. Herein, we report the optimization of some bis-unsymmetric dibasic tetradentate N2O2 oxo-titanium (IV) Schiff base complexes based on density functional theory. All the compounds were optimized at B3LYP/6-31G (d) level of theory. Frontier molecular orbital features, thermodynamic properties, dipole moment, electrostatic potential were investigated. All the compounds were subjected for molecular docking against beta-lactamase (BlaC) protein (3ZHH) to search binding affinity, binding mode(s). Molecular dynamics simulation was performed for the best bounded complex (C3) to observe the stability of protein-drug complexes. It was observed that all compounds were thermodynamically stable, while the addition of metal oxide increases thethermochemical stability, dipole moment, and chemical softness. Molecular docking and non-bonding interactions result disclosed the significant binding and interactions of some compounds with the receptor protein. ADMET calculations suggesting, all the compounds are non-carcinogenic and safe for biological use. Finally, this study may be helpful to design of new anti-tuberculosis agent.