Pharmacophore-based 3D-QSAR of HIF-1 inhibitors

被引：0
作者：
Jae Yoon Chung
F. A. Pasha
Seung Joo Cho
Misun Won
Jung Joon Lee
Kyeong Lee
机构：
[1] Korea Institute of Science and Technology,Department of Cellular and Molecular Medicine, College of Medicine
[2] Chosun University,undefined
[3] Korea Research Institute of Bioscience and Biotechnology,undefined
来源：
Archives of Pharmacal Research | 2009年 / 32卷
关键词：
CoMFA; CoMSIA; Drug design; Pharmacophore; HIF-1 Inhibitor; 3D-QSAR;
D O I：
暂无
中图分类号：
学科分类号：
摘要：
(Aryloxyamino)benzoic acids and nicotinic/isonicotinic acids represent an important new class of small molecules that inhibit the activation of Hypoxia-Inducible Factor (HIF)-1. In order to understand the factors affecting inhibitory potency of HIF-1 inhibitors, 3 dimensional-quantitative structure activity relationship (3D-QSAR) studies were performed. Since no receptor structure are available, the pharmacophore-based alignment was used for comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA). The CoMFA and CoMSIA models gave reasonable statistics (CoMFA: q2 = 0.564, r2=0.945; CoMSIA: q2 = 0.575, r2=0.929). Both CoMFA and CoMSIA results indicate that the steric interaction is a major factor, while CoMSIA suggests importance of hydrogen bonding. These findings about steric and H-bonding effects can be useful to design new inhibitors.
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页码：317 / 323
页数：6
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