物理化学学报 >> 2003, Vol. 19 >> Issue (01): 79-81.doi: 10.3866/PKU.WHXB20030118

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吡咯烷类胞液型磷脂酶A2抑制剂的比较分子力场分析

黄常康;高莹;刘振明;刘莹;来鲁华   

  1. 北京大学化学与分子工程学院,分子动态与稳态结构国家重点实验室,北京 100871
  • 收稿日期:2002-04-19 修回日期:2002-06-06 发布日期:2003-01-15
  • 通讯作者: 来鲁华 E-mail:lai@mdl.ipc.pku.edu.cn

Comparative Molecular Field Analysis of Pyrrolidine Inhibitors for Human Cytosolic Phospholipase A2

Huang Chang-Kang;Gao Ying;Liu Zhen-Ming;Liu Ying;Lai Lu-Hua   

  1. State Key Laboratory for Structural Chemistry of Unstable and Stable Species, College of Chemistry and Molecular Engineering, Peking University, Beijing 100871
  • Received:2002-04-19 Revised:2002-06-06 Published:2003-01-15
  • Contact: Lai Lu-Hua E-mail:lai@mdl.ipc.pku.edu.cn

摘要: 胞液型磷脂酶A2能引发关节炎,针对胞液型磷脂酶A2的抑制剂有可能成为治疗关节炎的特效药,因此引起了广泛的关注.文章对于吡咯烷类胞液型磷脂酶A2抑制剂进行了三维定量构效关系研究,利用比较分子力场分析构建了该类分子的定量构效关系,得到三维等值线图,为胞液型磷脂酶A2抑制剂的进一步改造提供了有益的启示.

关键词: 比较分子力场分析(CoMFA), 胞液型磷脂酶A2(cPLA2), 吡咯烷类抑制剂

Abstract: Cytosolic phospholipase A2 is consided as an important fact that will induce arthritis. We have studied the three-dimensional quantitative structure activity relationship for a series of reported pyrrolidine based inhibitors by the comparative molecular field analysis. One representative compound of the series 1a was docked onto cPLA2 (PDBcode: 1CJY) by using Dock and Autodock program to determine the most likely binding conformation to cPLA2. The strategy of all-placement search was used in the CoMFA study to give a final model with the cross-validation q2 of 0.701 and the total analysis of the CoMFA coefficients map gives insights to the design of better cPLA2 inhibitors.

Key words: Comparative molecular field analysis(CoMFA), Cytosolic phospholipaseA2 (cPLA2), Pyrrolidine inhibitor