Journal of Chemical and Pharmaceutical Research (ISSN : 0975-7384)

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Original Articles: 2016 Vol: 8 Issue: 10

Insilico Identification of Novel Inhibitors for Shikimate Kinase from Mycobacterium Tuberculosis using Natural and Synthetic Ligands

Abstract

Tuberculosis (TB) remains as a causes of death due to Mycobacterium tuberculosis. Tuberculosis (TB) is a major global health problem. It causes ill-health among millions of people each year and ranks alongside with human immunodeficiency virus (HIV) as a leading cause of death worldwide. Thus, the objective of this study was to determined novel inhibitors of Shikimate kinase from Mycobacterium tuberculosis (MTB) with aim of providing novel therapeutic candidates for treatment of tuberculosis in human. To understand the binding mode analysis and structural features, Shikimate kinase was modelled through homology modeling using Modeller 9.16. The modelled structures was validated using Ramachandran plot which revealed that 97.3% (142/146amino acid) of the entire residues lay in the most favourable regions [A, B, L], 2.7% (4/146amino acid) were in Additional allowed regions [a,b,l,p], while the none of the amino acid residues were found in both Generously allowed regions [~a,~b,~l,~p] and Disallowed regions[XX]. Validation with Pros A server shows a Z-Score of -8.44 which clearly indicates good quality model with high structural integrity, resembling structure determined through Nuclear Magnetic Resonance. The result of docking studies (synthetic ligands) among the several ligands used shows that, only thirteen (13) found to have promising activity against Shikimate kinase with a minimum free binding energy ranges from -11.52 and -9.00kcal/mol, while six natural ligands possess high activities with minimum free binding energy ranges from -11.75 and -8.49 kcal/mol. Therefore, these ligands were recommended for future drugs for the treatment of tuberculosis in human cause by both multidrug-resistant tuberculosis (MDR-TB) strain and extensive drug resistant strain