Citation: QIAO Kang, ZENG Ling-Xiao, JIN Hong-Wei, LIU Zhen-Ming, ZHANG Liang-Ren. QSAR Analysis of Human Adenosine A₃ Receptor Anta nists[J]. Acta Physico-Chimica Sinica, ;2012, 28(06): 1509-1519. doi: 10.3866/PKU.WHXB201203272 shu

QSAR Analysis of Human Adenosine A₃ Receptor Anta nists

1.
State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, P. R. China

Received Date: 22 February 2012
Available Online: 27 March 2012
Fund Project: 国家自然科学基金(20972010) (20972010)教育部博士点基金(20090001120049)资助项目 (20090001120049)

Ligand-based and receptor-based methods were implemented together to investigate the binding modes of human adenosine A₃ anta nists. First, pharmacophore models were developed using the HypoGen program with a training set of 18 diverse human adenosine A₃ receptor anta nists 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 anta nists and antiasthmatic compounds.
- Pharmacophore modeling,
- Homology modeling,
- Molecular docking,
- Virtual screening,
- Human adenosine A₃ receptor,
- Anta nists
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QSAR Analysis of Human Adenosine A₃ Receptor Anta nists