Acta Chimica Sinica ›› 2009, Vol. 67 ›› Issue (21): 2457-2462. Previous Articles     Next Articles

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雌激素β受体喹啉类配体的分子对接及3D-QSAR研究

李建a,b   梅虎*,a,b    龙云c    刘丽a,b    杨力a,b   

  1. (a生物流变科学与技术教育部重点实验室 重庆 400044) (b重庆大学生物工程学院 重庆 400044) (c西南大学生命科学学院 重庆 400075)
  • 投稿日期:2009-01-21 修回日期:2009-04-30 发布日期:2009-07-01
  • 通讯作者: 梅虎 E-mail:meihu@126.com

Molecular Docking and 3D-QSAR Research of Quinoline De-rivatives as Estrogen Receptor β Ligands

Li, Jian a,b    Mei, Hu *,a,b      Long, Yun c       Liu, Li  a,b      Yang, Li  a,b   

  1. (a Key Laboratory of Biorheological Science and Technology (Ministry of Education), Chongqing University, Chongqing 400044) (b College of Bioengineering, Chongqing University, Chongqing 400044) (c School of Life Sciences, Southwest University, Chongqing 400075)
  • Received:2009-01-21 Revised:2009-04-30 Published:2009-07-01

The molecular docking followed by comparative molecular field analysis (CoMFA) and comparative molecular similarity index analysis (CoMSIA) was employed to the three-dimensional quantitative structure-activity relationship (3D-QSAR) studies of estrogen receptor-β of 33 quinoline derivatives. A significant correlation coefficient was obtained between total scores and binding affinities. The results showed that the hydrogen-bonding interactions between the hydroxy group of chromane and quinoline ring and the receptor, hydrophobic interactions between the ligand and the active site of estrogen receptor-β, and electronic interactions between the ligand and the Arg346 and Glu305 residuals were the dominant factors affecting the binding affinities. Besides, the steric effect of substituting group of quinoline ring also affected the binding activities. Based on the docking conformations, CoMFA and CoMSIA were employed to the QSAR studies of 33 quinoline derivatives. The number of principal components, r2, q2 (leave-one-out, LOO), of the optimal CoMSIA model were 6, 0.958, 0.669 and 0.741 respectively. The conclusions obtained from contour map analysis were in agreement with the docking results.

Key words: QSAR, CoMFA, CoMSIA, molecular docking, quinoline, estrogen receptor-β