Docking Studies of N-alkylated Indole chalcone derivatives with Mycobacterium tuberulosis Enoyl Acyl Carrier Protein Reductase (Inh A) as Potent Antitubercular agents

The worrisome rise in multi and extensively drug-resistant Mycobacterium tuberculosis strains has prompted researchers to look for new, more effective, and safer treatments. A variety of N-alkylated indole chalcone derivatives were docked against the InhA enzyme to achieve this goal. In the present study, the flexible ligand docking simulations were performed on 88 new compounds against the InhA protein with the PDB ID-4TZK by using Glide module. All the docks are considered as well docked as all of them were bound to Ligand binding domain of InhA. The InhA was identified through an in silico docking investigation as a possible molecular target for the N-alkylated indole chalcone derivatives. This work sought to identify possible inhibitors of the Enoyl-ACP reductase (InhA), which regulates the formation of the cell wall in mycobacterium, using in silico methods. Most of the compounds show good Glide score compare to INH as reference drug. Compound (E)-1-(4-bromo-2-hydroxyphenyl)-3(1-butyl-1H-indol-3-yl) prop-2-en-1-one (S1R8) showed highest GLIDE score (-10.45), (S1R16-10.41), (S1R22-10.17) and (SIR24-10.10) compared to INH (-7.15). The presence of oxygen group in the ring showed hydrogen bond interactions with NAD and Tyr158 residues. Results obtained are valuable for synthesis and therefore biological screening of promising hits.