Discovery of Potential Integrin VLA-4 Antagonists Using Pharmacophore Modeling, Virtual Screening and Molecular Docking Studies

Authors

  • Sundarapandian Thangapandian,

    1. Department of Biochemistry and Division of Applied Life Science (BK21 Program), Environmental Biotechnology National Core Research Center, Gyeongsang National University, 900 Gazwa-dong, Jinju 660-701, Korea
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  • Shalini John,

    1. Department of Biochemistry and Division of Applied Life Science (BK21 Program), Environmental Biotechnology National Core Research Center, Gyeongsang National University, 900 Gazwa-dong, Jinju 660-701, Korea
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  • Sugunadevi Sakkiah,

    1. Department of Biochemistry and Division of Applied Life Science (BK21 Program), Environmental Biotechnology National Core Research Center, Gyeongsang National University, 900 Gazwa-dong, Jinju 660-701, Korea
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  • Keun Woo Lee

    Corresponding author
      Corresponding author: Keun Woo Lee, kwlee@gnu.ac.kr
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Corresponding author: Keun Woo Lee, kwlee@gnu.ac.kr

Abstract

Very late antigen-4 (VLA-4) is an integrin protein, and its antagonists are useful as anti-inflammatory drugs. The aim of this study is to discover novel virtual lead compounds to use them in designing potent VLA-4 antagonists. A best pharmacophore model was generated with correlation coefficient of 0.935, large cost difference of 114.078, comprising two hydrogen bond acceptors and three hydrophobic features. It was further validated and used in database screening for potential VLA-4 antagonists. A homology model of VLA-4 was built and employed in molecular docking of screened hit compounds. Finally, two compounds were identified as potential virtual leads to be deployed in the designing of novel potent VLA-4 antagonists.

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