新型查尔酮衍生物抗乳腺癌活性的3D-QSAR模型构建及分子设计  

3D-QSAR model for anti-breast cancer activity of novel chalcones derivatives and their molecular design

作　　者：陈艳[1] 冯惠 冯长君[1] 堵锡华[1] Chen Yan;Feng Hui;Feng Changjun;Du Xihua(School of Material and Chemical Engineering,Xuzhou Institute of Technology,Xuzhou 221018,China)

机构地区：[1]徐州工程学院材料与化学工程学院,江苏徐州221018

出　　处：《南京理工大学学报》2024年第2期248-252,共5页Journal of Nanjing University of Science and Technology

基　　金：国家自然科学基金(21472071);江苏省自然科学基金(BK20171169)。

摘　　要：为了获得较高抗乳腺癌活性的新型化合物,对18个新型查尔酮衍生物抗乳腺癌活性(pIC_(50))进行了三维定量构效关系(3D-QSAR)研究。其中14个化合物作为训练集用于构建3D-QSAR模型,其余化合物(含模板分子)作为测试集对所建模型进行验证。所建3D-QSAR模型的交叉验证系数R^(2)_(CV)为0.569,非交叉验证系数R^(2)为0.974,说明所建模型具有良好的稳定性和预测能力。该模型中立体场、静电场对pIC_(50)的贡献分别为58.8%和41.2%,表明影响该类化合物抗肿瘤活性的主要因素是取代基的疏水性、空间位阻和电荷分布。通过对模型的分析,设计了5个具有较高pIC_(50)的新化合物,有待通过后续医学实验加以验证。In order to obtain novel compounds with high anti-breast cancer activity,three dimensional quantitative structure-activity relationships(3D-QSAR)between the structure of the anti-breast cancer activity(pIC_(50))of 18 novel chalcone derivatives is studied.The 3D-QSAR models are built using fourteen compounds in the training set,which are verified by the test set of other compounds(containing template molecule).The cross-validation coefficient R^(2)_(CV) of the 3D-QSAR model is 0.569,and the non-cross-validation coefficient R^(2) is 0.974.It indicates that the model has good stability and predictive ability.In this model,the contribution of stereoscopic field and electrostatic field to pIC_(50) are 58.8% and 41.2%,respectively,indicating that hydrophobicity,steric hindrance and charge distribution are the main factors affecting the pIC_(50).Through the analysis of the model,five new compounds with high pIC_(50) are designed,which need to be verified by future medical experiments.

关 键 词：新型查尔酮衍生物 抗乳腺癌活性 三维定量构效关系 分子设计 

分 类 号：R979.1[医药卫生—药品]