Molecular Docking Study of New Pyrrolyl Benzohydrazide Schiff Bases as M. tuberculosis InhA Enzyme Inhibitors

Abstract

Background Tuberculosis TB is an ancient chronic infectious disease affecting primarily the lungs of humans and rapidly co-evolved with humans since several million years. It is mainly caused by a group of bacterial species termed Mycobacterium tuberculosis a principal strain of this infection. Each second millions are at risk of acquiring new infection of becoming sick prone to death and a conclusive understanding of pathogenesis is still deficient.Objective To design a series of new pyrrole benzohydrazide schiff bases as M. tuberculosis InhA inhibitors.Methods Docking software Sybyl-X version 2.0 was used for molecular modeling. To dock intended compounds Surflex-Dock procedure of sybyl was castoff. M. tuberculosis enoyl reductase InhA inhibitor target protein 4TZK complexed with ligand 1-cyclohexyl-N-3 5-dichlorophenyl-5-oxopyrrolidine3-carboxamide was taken from Protein Data Bank PDB entry code 4TZK httpwww.rcsb.orgpdb.Results Docking scores of the compounds ranged between 5.47 - 3.32 summarizing the interface force field between enzyme and the ligands.Conclusion Sixteen molecules bearing pyrrole hydrazone moiety were docked showing promising M. tuberculosis inhibition activity. In silico molecular docking analysis exhibited that peptide linkage -CO-NH- and imine -CN- of pyrrole hydrazones were important in binding with the targeted receptor.