天然产物研究与开发 ›› 2016, Vol. 28 ›› Issue (5): 643-649.doi: 10.16333/j.1001-6880.2016.5.001

• 研究论文 •    下一篇

裂木质素类化合物与5α-还原酶的构效关系研究

李小奇,曹洪玉,于大永*,冯宝民*   

  1. 大连大学生命科学与技术学院,大连 116622
  • 出版日期:2016-05-28 发布日期:2016-09-06

3D-QSAR Studies on Secolignansas as 5-alpha Reductase Inhibitors

LI Xiao-qi,CAO Hong-yu,YU Da-yong*,FENG Bao-min*   

  1. School of Life Science and Technology,Dalian University,Dalian 116622,China
  • Online:2016-05-28 Published:2016-09-06

摘要: 5α-还原酶(5α-reductase,5-AR)是治疗良性前列腺增生的关键酶。前期研究发现裂木质素类化合物有抑制5-AR的作用,为了深化对荨麻属裂木质素类植物的研究,并探索裂木质素类抑制剂对5-AR的抑制作用及二者构效关系,采用同源模建的方法构建5-AR的三维空间结构模型,并利用Ramachandran plot、verify3D和ERRAT程序对模型进行评价,同时通过分子力学等方法对最优模型进行优化。利用分子对接的方法将5-α还原酶抑制剂(5α-reductase inhibitors,5-ARI)对接到12个活性位点,其中5个位点与配体对接成功,并预测了41种裂木质素化合物的ADMET性质。本文研究结果对裂木质素类化合物的药物设计具有一定的理论指导作用,并且为良性前列腺增生的治疗研究提供新思路。

关键词: 荨麻属植物, 裂木质素化合物, 5-AR, 5-ARI, 同源模建, 分子对接, ADMET预测

Abstract: 5-Alpha reductase (5-AR) is a key enzyme in the treatment of benign prostatic hyperplasia.Previous studies found that the secolignansas had effect on the 5-AR as inhibitor.In order to study the nettle genus plant and explore the relationship between 5-AR and nonsteroidal inhibitor ecolignans.Homology modeling method was applied to build the three dimensional structure of 5-AR.The obtained protein structure was evaluated by Ramachandran Plot,verify3D and ERRAT program,and optimized by molecular mechanics methods.The optimal protein structure was used for the molecular docking test,the 5-alpha reductase inhibitors were ligands,docked into the active binding sites.The docking data and chart demonstrated that there were 12 binding sites,and 5 of them docked successfully.In addition,41 Secolignansas compounds properties were predicted by ADMET.These results provided the guidance to design new drugs,as well as new ideas for the treatment of benign prostatic hyperplasia.

Key words: nettle genus;5-&alpha, reductase;5-&alpha, reductase inhibitors;homology modeling;docking;ADMET prediction

中图分类号: 

R914