Pharmacokinetic and Molecular docking studies of Centella asiatica phytocompounds to explore potential anti-tuberculosis activity

Abstract

Tuberculosis is caused by the bacterium Mycobacterium tuberculosis. The first line drugs available for treatment of TB are isoniazid, rifamsin etc. Second line drugs are Paraminosalicylate, kanamycin etc. Numerous reports have demonstrated the cause and emergence of multi-drug resistance of Mycobacterium tuberculosis.It is necessary to discover new drugs to control these new strains of M.tuberculosis. Computer aided drug discovery(CADD) is a new approach to discover new drugs from plants or other sources by the help of digital technologies. First step of this process is to select a suitable drug target. Next screening of the ligand against these targets to determine the binding affinities of these ligands and receptors. In this study, the two enzymes of Mycobacterial shikimate pathway shikimate dehydrogenase and chorismate synthase were selected as drug targets. The 6 phytocompounds from traditionaly used medicinal plant Centella asiatica was screnned against these targets. Molecular docking study was done to check the receptor(protein)-ligand (phytocompounds) binding. The result of molecular docking study shows the diffrent binding affinities of these phytocompounds with these two enzymes. So these phytocompounds may inhibit the activity of these two enzymes and may block the shikimate pathway of M.tuberculosis. Later , to establish as drug molecules pharmacokinetic analysis of these phytocompounds was done. All these phytocompounds have drug like properties , they obey Lipinski’s rule of 5 and have less toxicity.