Biotechnology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.
Iran J Basic Med Sci. 2013 Aug;16(8):910-6.
OBJECTIVE(S): The structure- activity relationship of a series of 36 molecules, showing L-type calcium channel blocking was studied using a QSAR (quantitative structure-activity relationship) method.
Structures were optimized by the semi-empirical AM1 quantum-chemical method which was also used to find structure-calcium channel blocking activity trends. Several types of descriptors, including electrotopological, structural and thermodynamics were used to derive a quantitative relationship between L-type calcium channel blocking activity and structural properties. The developed QSAR model contributed to a mechanistic understanding of the investigated biological effects.
Multiple linear regressions (MLR) was employed to model the relationships between molecular descriptors and biological activities of molecules using stepwise method and genetic algorithm as variable selection tools. The accuracy of the proposed MLR model was illustrated using cross-validation, and Y-randomisation -as the evaluation techniques.
The predictive ability of the model was found to be satisfactory and could be used for designing a similar group of 1,4- dihydropyridines , based on a pyridine structure core which can block calcium channels.
使用定量构效关系（QSAR）方法研究了一系列 36 种分子的结构-活性关系，这些分子表现出 L 型钙通道阻断作用。
采用半经验 AM1 量子化学方法对结构进行优化，该方法还用于寻找结构-钙通道阻断活性趋势。使用几种类型的描述符，包括电拓扑、结构和热力学，来推导出 L 型钙通道阻断活性与结构特性之间的定量关系。所开发的 QSAR 模型有助于对所研究的生物效应的机制理解。
使用逐步法和遗传算法作为变量选择工具，采用多元线性回归（MLR）将分子描述符与分子的生物活性之间的关系进行建模。使用交叉验证和 Y 随机化作为评估技术来说明所提出的 MLR 模型的准确性。
该模型的预测能力令人满意，可用于设计基于吡啶结构核心的类似组 1,4-二氢吡啶，该核心可阻断钙通道。
