Abstract

Tuberculosis (TB) remains a global health threat, with increasing resistance to first-line drugs like isoniazid necessitating the discovery of novel therapeutics. This study focuses on the in-silico evaluation of 11 novel compounds of oxindole-triazole tethered derivatives (NV1–NV11) against the catalase peroxidase enzyme of Mycobacterium tuberculosis (PDB ID: 1SJ2). Molecular docking was performed to evaluate binding scores, revealing that compound NV10 exhibited the strongest interaction with a high binding affinity of −10.262 (kcal/mol), showing a more favorable docking score than isoniazid (−6.331 kcal/mol). Molecular dynamics simulations (MDS) over 100 ns confirmed the structural stability and compactness of the NV10-1SJ2 complex, supported by stable RMSD, RMSF, and radius of gyration profiles. MM-GBSA binding free energy calculations further validated NV10's binding energy, with a favorable ΔG_bind of −68.21 ± 3.10 kcal/mol, primarily given by van der Waals and Coulombic interactions. These results suggest that NV10 is a computationally promising compound for developing new anti-TB agents.

Key words: Molecular Docking, Molecular Dynamics, Oxindole, Triazole, Tuberculosis