Computational evaluation of novel Schiff base compounds targeting Mycobacterium tuberculosis

Abstract

Background/Aim Tuberculosis remains a major global health concern and continues to pose significant challenges to global public health. Key enzymes involved in mycobacterial cell wall biosynthesis, including DprE1, InhA, KasA, MmpL3, and LdtMt2, represent attractive therapeutic targets for anti-tubercular drug discovery. The present study aimed to evaluate the binding potential of newly designed coumarin Schiff base derivatives against selected Mycobacterium tuberculosis protein targets using molecular docking to identify compounds for further investigation as potential anti-tubercular candidates. Methods Novel Schiff base derivatives were evaluated for oral drug-likeness using Lipinski's rule and in silico ADMET/toxicity profiling. Protein structures were validated using Ramachandran plots, and active-site residues were identified. Molecular docking analysis was performed against five tuberculosis-associated protein targets (4P8T, 2NSD, 2WGD, 7NVH, and 5 DC2) to assess binding affinities and interaction profiles. Results Docking studies revealed that SB5, SB13, and SB21 exhibited favorable binding interactions with all selected targets through hydrogen bonding, van der Waals forces, and hydrophobic interactions involving key residues such as HIS, TYR, SER, ASN, and GLY. Among these, SB21 demonstrated comparatively better binding energies (−10.3 to −8.1 kcal/mol), particularly against 2NSD (−10.5 kcal/mol), along with favorable in silico toxicity characteristics. Conclusion SB5, SB13, and SB21 emerged as promising preliminary anti-tubercular lead candidates. However, further validation through molecular dynamics simulations and experimental studies is required to confirm their therapeutic relevance.