引用本文:
【打印本页】   【HTML】   【下载PDF全文】   View/Add Comment  【EndNote】   【RefMan】   【BibTex】
←前一篇|后一篇→ 过刊浏览    高级检索
本文已被:浏览 1168次   下载 1163 本文二维码信息
码上扫一扫!
分享到: 微信 更多
Quantitative Structure-Activity Relationship of Quinazoline Derivatives with the Inhibitory Activity Toward NF-κB
Wu Wenjuan1,2, Chen Jincan1, Zheng Kangcheng*1, Yun Fengcun1
1.School of Chemistry and Chemical Engineering, Sun Yat-Sen University, Guangzhou 510275;2.Department of Physical Chemistry, Guangdong Pharmaceutical College, Guangzhou 510224
Abstract:
The electronic structures, geometric structures and some molecular properties (generalized structural indexes) of quinazoline derivatives were computed by using density functional theory and molecular mechanism methods to investigate the quantitative structure-activity relationship (QSAR) of the inhibitory activity toward the nuclear factor kappa B. Via a stepwise regression analysis, some main factors affecting the activity of the compounds were factored out, and then the QSAR equation was effectively established. It was found that the hydrophobic parameter of the substituent on ring D is the main factor affecting the inhibitory activity of the compound. The analysis indicated, the larger the hydrophobic parameter, the higher the inhibitory activity of the compound. In addition, the net charge of the first atom and the stereoscopic parameter (MR1) of the substituent R1 on A-ring as well as the net charge of C3 are closely correlated with the inhibitory activity of the compound. In order to test the predicted results of the QSAR equation, we adopted the “leave one out” cross-validation , and found that the calculated coefficient q2 was rather high and the predicted results were both accurate and reliable. Such facts show that the obtained equation has great predictive ability. The above results can offer an important theoretical guide in the search for new quinazoline derivatives with higher inhibitory activity, and in an analysis of their action mechanisms. It is noteworthy that this scheme would be very advantageous in factoring out precursors with excellent inhibitory activity via the computer ADDIT molecule-design, since all parameters in the QSAR equation are computable and controllable.
Key words:  Quinazoline derivative, Nuclear factor kappa, Activation-inhibitor, Density functional theory, Quantitative structure-activity relationship
FundProject:
核因子κB活性抑制剂定量构效关系
吴文娟1,2, 陈锦灿1, 郑康成*1, 云逢存1
1.中山大学化学与化学工程学院,广州,510275;2.广东药学院物理化学教研室,广州,510224
摘要:
用量子化学密度泛函及分子力学方法,计算了一系列喹唑啉衍生物分子的电子结构、几何结构及分子性质(广义结构)的各种参数,用以探讨该类药物分子的结构与对核因子抑制活性的关系.通过逐步回归分析,筛选出主要因素,建立了定量构效关系方程.结果表明,化合物的环D上17位碳原子上的取代基X的疏水参数、环A中R1取代基上第一个原子的净电荷及该取代基的立体参数,以及环A上3位碳原子的净电荷与化合物的抑制活性紧密相关,它们是影响化合物抑制活性的主要因素.采用"leave one out"法进行预报检验,其交叉检验相关系数较大,
关键词:  喹唑啉衍生物  核因子κB  活性抑制剂  密度泛函法  定量构效关系
DOI:10.1088/1674-0068/18/6/936-940
分类号: