In Silico Docking Analysis of Mycobacterium Tuberculosis Potential Targets of Enoyl-Acp Reductase (INHA) with Transition Metals Complex Ligand

Munusamy Jambulingam, Subramaniam AnandaThangadurai, Manickam Vijayabaskaran 1

8th WCPSDM.2021. APR.Published Online 18 APR 2021

Abstract : Human tuberculosis (TB), caused by Mycobacterium tuberculosis, is the leading bacterial killer disease worldwide and new anti-TB drugs are urgently needed. The current use of antibiotics used to treat TB causes difficulties such as : (i) the emergence of multidrug-resistant (MDR) strains of M. tuberculosis, and (ii) the persistent state of the bacterium, which is less susceptible to antibiotics and causes very long antibiotic treatment regimes. It is a disease that cannot be cured through conventional remedies. In the current study, homology model of the targets were designed. Five metal complex ligands which were synthesized from salicylaldehyde and histidine, the schiff base obtained were condensed with various metal chlorides such as CuCl2, ZnCl2, FeCl2, MnCl2 and CoCl2 in the ratio: of 2:1 and were docked with the selected potential target of Mycobacterium tuberculosis (1BVR) Enoyl-Acp Reductase (INHA) . The primary docking analysis was performed through discover studio which is then validated through AutoDock Vina docking software. The active sites were also predicted through the Ligands tools. These metal complex ligands had a significant inhibitory activity with the receptor. The Binding pocket for the targets were predicted for 1BVR (PRO A 59, GLY A183, ARG A09, GLN A 35, GLUA8 0, ARG A 112 ) forming hydrogen bonds at a very low energy value, thus forming a stable complex. The cobalt metal ligand had excellent conformations showing the flexible behaviour of the ligand. The minimum binding energy of cobalt complex with Enoyl-Acp Reductase (INHA) is -10.7 kcal/mol and isoniazid is -8.73 kcal/mol, which indicated that the cobalt metal complex has showed significant anti tubercular activity when compared to the standard isoniazid.