基于比较分子场分析的PU3类似物的3D-QSAR研究。

3D-QSAR studies on PU3 analogues by comparative molecular field analysis.

作者信息

Liu Hong-Chong, Lyu Ping-Chiang, Leong Max K, Tsai Keng-Chang, Hsiue Ging-Ho

机构信息

Institute of Biomedical Sciences, National Chung Hsing University, Taichung, Taiwan 402, ROC.

出版信息

Bioorg Med Chem Lett. 2004 Feb 9;14(3):731-4. doi: 10.1016/j.bmcl.2003.11.024.

DOI:10.1016/j.bmcl.2003.11.024

PMID:14741278

Abstract

A comparative molecular field analysis (CoMFA) of PU3 derivatives of Hsp90 (Heat shock protein 90) inhibitors has been performed to determine the factors contributing the corresponding activities. The energy minimized conformations were obtained by molecular mechanics using SYBYL package. The developed model, with r(2) value of 0.947, was verified by performing leave-one out (LOO) cross-validation, which showed q(2) value of 0.513. The calculated model not only elucidates the relationship between compound structures and biological activities but, more importantly, facilitates design of new Hsp90 inhibitors with calculated antiproliferative activity.

摘要

已对热休克蛋白90（Hsp90）抑制剂的PU3衍生物进行了比较分子场分析（CoMFA），以确定影响相应活性的因素。使用SYBYL软件包通过分子力学获得能量最小化构象。通过留一法（LOO）交叉验证对所建立的模型进行了验证，其r(2)值为0.947，q(2)值为0.513。所计算的模型不仅阐明了化合物结构与生物活性之间的关系，更重要的是，有助于设计具有计算出的抗增殖活性的新型Hsp90抑制剂。