title: Ligand based virtual screening and biological evaluation of inhibitors of chorismate mutase (Rv1885c) from Mycobacterium tuberculosis H37Rv.
abstract: We have identified new lead candidates that possess inhibitory activity against Mycobacterium tuberculosis H37Rv chorismate mutase by a ligand-based virtual screening optimized for lead evaluation in combination with in vitro enzymatic assay. The initial virtual screening using a ligand-based pharmacophore model identified 95 compounds from an in-house small molecule database of 15,452 compounds. The obtained hits were further evaluated by molecular docking and 15 compounds were short listed based on docking scores and the other scoring functions and subjected to biological assay. Chorismate mutase activity assays identified four compounds as inhibitors of M. tuberculosis chorismate mutase (MtCM) with low K(i) values. The structural models for these ligands in the chorismate mutase binding site will facilitate medicinal chemistry efforts for lead optimization against this protein.
authors.affiliation: Molecular and Structural Biology, Central Drug Research Institute, Lucknow 226 001, India.
authors.forename: Himanshu
authors.initials: H
authors.lastname: Agrawal
authors.forename: Ashutosh
authors.initials: A
authors.lastname: Kumar
authors.forename: Naresh Chandra
authors.initials: NC
authors.lastname: Bal
authors.forename: Mohammad Imran
authors.initials: MI
authors.lastname: Siddiqi
authors.forename: Ashish
authors.initials: A
authors.lastname: Arora
mesh_terms: D000465:Algorithms; D000995:Antitubercular Agents / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology; D001426:Bacterial Proteins / Q000037:antagonists & inhibitors*; D002826:Chorismate Mutase / Q000037:antagonists & inhibitors*; D016208:Databases, Factual; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology; D008024:Ligands; D009169:Mycobacterium tuberculosis / Q000201:enzymology*; D012984:Software; D013329:Structure-Activity Relationship
chemical_list: D000995:Antitubercular Agents; D001426:Bacterial Proteins; D004791:Enzyme Inhibitors; D008024:Ligands; D002826:Chorismate Mutase