Ligand based virtual screening and biological evaluation of inhibitors of chorismate mutase (Rv1885c) from Mycobacterium tuberculosis H37Rv

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• 作者：Himanshu Agrawal ; Ashutosh Kumar ; Naresh Ch ; ra Bal ; Mohammad Imran Siddiqi ; Ashish Arora
• 关键词：Mycobacterium tuberculosis ; Chorismate mutase ; Virtual screening ; Molecular docking ; Biological evaluation
• 刊名：Bioorganic and Medicinal Chemistry Letters
• 出版年：2007
• 出版时间：1 June 2007
• 年：2007
• 卷：17
• 期：11
• 页码：3053-3058
• 全文大小：700 K

文摘

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.