3D-QSAR and Surflex Docking Studies of a Series of Alkaline Phosphatase Inhibitors

论文摘要

Alkaline phosphatases（APs） include the placental AP（PLAP）, germ cell AP（GCAP）, intestinal AP（IAP） and tissue nonspecific AP（TNAP）. Over expression of TNAP in smooth muscle cells of kidney and vessels provokes the progress of such serious diseases as end-stage renal disease, idiopathic infantile arterial calcification, ankylosis, osteoarthritis and diabetes. In order to design and optimize the potent TNAP inhibitors, comparative molecular field analysis（CoMFA） and comparative molecular similarity indices analysis（CoMSIA） were used to analyze 3D structure-activity relationships（3D-QSAR） of TNAP inhibitors. The 3D-QSAR model（CoMFA with q2 = 0.521, r2 = 0.930; CoMSIA with q2 = 0.529, r2 = 0.933） had a good predictability. Surflex-dock was used to reveal the binding mode between the inhibitors and TNAP protein. CoMFA, CoMSIA and docking results provide guidance for the discovery of TNAP inhibitors. Finally, eight new compounds as potential TNAP inhibitors were designed.

论文目录

1 INTRODUCTION

2 MATERIALS AND METHODS

2.1 Compounds and activities

2.2 Minimization and alignment

2.3 CoMFA and CoMSIA procedures

2.4 Docking studies

3 RESULTS AND DISCUSSION

3.1 Evaluation of the model validity

3.2 3D Contour maps analysis

3.3 Docking study

3.4 Design of new molecules

4 CONCLUSION

文章来源

类型: 期刊论文

作者: 舒茂,武涛,王必武,李静,徐春媚,林治华

来源: Chinese Journal of Structural Chemistry 2019年01期

年度: 2019

分类: 工程科技Ⅰ辑

专业: 有机化工

单位: School of Pharmacy and Bioengineering,Chongqing University of Technology

基金: supported by the Key Project of Natural Science Foundation of Chongqing(No.cstc2015jcyjBX0080),Science and Technology project of Chongqing Education Commission(KJ1600907)

分类号: TQ460.1

DOI: 10.14102/j.cnki.0254-5861.2011-1917

页码: 7-16

总页数: 10

文件大小: 661K

下载量: 84

3D-QSAR and Surflex Docking Studies of a Series of Alkaline Phosphatase Inhibitors

论文摘要

论文目录

文章来源

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