Discovery of natural inhibitors targeting 2 - trans enoyl acyl carrier protein reductase in Mycobacterium tuberculosis by structure based drug designing

Abstract

Evolution and the rapid spread of the multidrug resistant Mycobacterium tuberculosis (Mtb) have posed a serious crisis. Moreover, the available first line drugs also confer adverse effects on the patients suffering from tuberculosis (TB) thus making the cure increasingly difficult. Thus the search of novel and potent natural compounds targeting anti-tubercular agents has become inevitable. Here, we report identification of potential natural anti-tubercular candidates targeting Mtb 2-Trans Enoyl Acyl Carrier Protein Reductase (InhA) of the fatty acid pathway using structure based drug designing. In the present study, we selected a total of 154 compounds from three plants i.e. Ginkgo biloba, Neem (Azadirachta indica) and Tea (Camellia sinensis) which were obtained from PubChem Compounds. These compounds were subjected to Lipinski’s rule of five and drug likeness filters. Finally, the compounds were docked at the active site of Mtb InhA (PDB code: 3FNE) using AutoDock Vina to select inhibitors with favourable interactions. The structure based ligand receptor docking aided in the identification of a number of natural candidates which had high binding affinities against Mtb InhA. Thus, these molecules could potentially inhibit Mtb InhA and succor to the development of lead compounds in the experimental drug discovery of anti-tuberculars.