Rasulev B F, Saidkhodzhaev A I, Nazrullaev S S, Akhmedkhodzhaeva K S, Khushbaktova Z A, Leszczynski J
Computational Center for Molecular Structure and Interactions, Jackson State University, 1235 J.R. Lynch Street, Jackson, MS 39217-0510, USA.
SAR QSAR Environ Res. 2007 Oct-Dec;18(7-8):663-73. doi: 10.1080/10629360701428631.
The relationship between chemical structure and estrogenic activity in a series of terpenoid esters with aromatic and aliphatic acid substituents isolated from Ferula plants, was studied. The fragments of the terpenoid structure that are potentially responsible for estrogenic activity were revealed. A quantitative structure-estrogenic activity study has been carried out using the QSAR approach with use of data derived from quantum-chemical calculations as well as data generated from three-dimensional structures of terpenoids. A number of molecular descriptors was obtained from the density functional theory (DFT) at the B3LYP/6-31G(d, p) level of calculation. Comparative analysis of the quantum-chemical computational data was also performed to confirm hypothesis concerning importance of the distance between the oxygen of alcohol hydroxyl group and the functional group in the para-position of the benzene ring (the hydroxyl or methoxy group). Use of the Genetic Algorithm in the QSAR analysis allowed the structural and physicochemical parameters of the terpenoids responsible for estrogenic activity to be determined. A significant QSAR model was obtained with an r(2) value of 0.892. The resulting model showed a reliable dependence of estrogenic activity of the terpenoids on such parameters as molecular shape, number of phenolic groups, surface polarity and the energy of the highest occupied molecular orbital.
研究了从阿魏属植物中分离出的一系列带有芳香酸和脂肪酸取代基的萜类酯的化学结构与雌激素活性之间的关系。揭示了萜类结构中可能与雌激素活性有关的片段。利用定量构效关系（QSAR）方法，结合量子化学计算数据以及萜类三维结构生成的数据，开展了定量结构-雌激素活性研究。在B3LYP/6-31G(d, p)计算水平上，通过密度泛函理论（DFT）获得了多个分子描述符。还对量子化学计算数据进行了比较分析，以证实关于醇羟基的氧与苯环对位官能团（羟基或甲氧基）之间距离的重要性的假设。在QSAR分析中使用遗传算法，确定了与雌激素活性有关的萜类的结构和物理化学参数。获得了一个显著的QSAR模型，r(2)值为0.892。所得模型表明，萜类的雌激素活性可靠地依赖于诸如分子形状、酚羟基数量、表面极性和最高占据分子轨道能量等参数。
