Molecular Design of Anticancer Drug Leads Based on Three-Dimensional Quantitative Structure-Activity Relationship

被引：22

作者：

Huang, Xiao Yan ^{[1
]}

Shan, Zhi Jie ^{[1
]}

Zhai, Hong Lin ^{[1
]}

Li, Li Na ^{[1
]}

Zhang, Xiao Yun ^{[1
]}

机构：

[1] Lanzhou Univ, Coll Chem & Chem Engn, Lanzhou 730000, Peoples R China

来源：

JOURNAL OF CHEMICAL INFORMATION AND MODELING | 2011年 / 51卷 / 08期

关键词：

MANIFEST ANTIPROLIFERATIVE ACTIVITY; NOVOBIOCIN ANALOGS; HSP90; INHIBITORS; CANCER; CHAPERONE; TARGET; HEAT-SHOCK-PROTEIN-90; GELDANAMYCIN; MODULATION; DOMAIN;

D O I：

10.1021/ci2002236

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Heat shock protein 90 (Hsp90) takes part in the developments of several cancers. Novobiocin, a typically C-terminal inhibitor for Hsp90, will probably used as an important anticancer drug in the future. In this work, we explored the valuable information and designed new novobiocin derivatives based on a three-dimensional quantitative structure activity relationship (3D QSAR). The comparative molecular field analysis and comparative molecular similarity indices analysis models with high predictive capability were established, and their reliabilities are supported by the statistical parameters. Based on the several important influence factors obtained from these models, six new novobiocin derivatives with higher inhibitory activities were designed and confirmed by the molecular simulation with our models, which provide the potential anticancer drug leads for further research.

引用

页码：1999 / 2006

页数：8

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