Acta Phys. -Chim. Sin. ›› 2012, Vol. 28 ›› Issue (06): 1509-1519.doi: 10.3866/PKU.WHXB201203272

• BIOPHYSICAL CHEMISTRY • Previous Articles     Next Articles

QSAR Analysis of Human Adenosine A3 Receptor Antagonists

QIAO Kang, ZENG Ling-Xiao, JIN Hong-Wei, LIU Zhen-Ming, ZHANG Liang-Ren   

  1. State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, P. R. China
  • Received:2012-02-22 Revised:2012-03-27 Published:2012-05-17
  • Contact: JIN Hong-Wei, ZHANG Liang-Ren;
  • Supported by:

    The project was supported by the National Natural Science Foundation of China (20972010) and Doctoral Fund of Ministry of Education of China (20090001120049).

Abstract: Ligand-based and receptor-based methods were implemented together to investigate the binding modes of human adenosine A3 antagonists. First, pharmacophore models were developed using the HypoGen program with a training set of 18 diverse human adenosine A3 receptor antagonists from literature. Meanwhile, the three-dimensional structure of A3 receptor was modeled by homology modeling and molecular dynamics, and validated by PROCHECK. Molecular docking was conducted further to investigate receptor-ligand interactions. The pharmacophore model and homology models of A3 receptor matched well, allowing some important information to be obtained. One of the new pharmacophore models was used to screen the MDL drug database report (MDDR) including about 120000 compounds. As a result, eight candidate compounds that can be used for biological evaluation were discovered. These findings are important for the development and discovery of novel selective A3 antagonists and antiasthmatic compounds.

Key words: Pharmacophore modeling, Homology modeling, Molecular docking, Virtual screening, Human adenosine A3 receptor, Antagonists


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