新的价键指数用于甲酰胺类似物活性的理论研究  

Theoretical study on activity of formamide analoguesby using new valence bond index

作　　者：堵锡华[1] 田林[1] 李靖[1] 宋明[1] 陈艳[1] 冯惠 DU Xi-hua;TIAN Lin;LI Jing;SONG Ming;CHEN Yan;FENG Hui(School of Materials and Chemical Engineering,Xuzhou University 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：《分子科学学报》2022年第3期234-241,共8页Journal of Molecular Science

基　　金：国家自然科学基金资助项目(21472071);江苏省自然科学基金(BK20171168);江苏省高校自然科学基金重大资助项目(18KJA430015)。

摘　　要：甲酰胺类化合物是重要的药物化学中间体,也是很多生物活性化合物的重要组成部分,被广泛应用于医药和农药等生产行业.为了研究4-羟氨基-α-吡喃酮甲酰胺类似物活性与其分子结构的定量构效关系,根据分子中原子的特性和连接性,提出了一种新的分子结构指数———价键指数B,并计算了42个4-羟氨基-α-吡喃酮甲酰胺类似物的电性距离矢量,筛选其中M_(14),M_(77)和M_(78)作为理论结构描述符,将其与价键指数B结合,与4-羟氨基-α-吡喃酮甲酰胺类似物活性进行回归分析,将4种参数作为神经网络法的输入层参数,采用4-4-1的神经网络结构,构建了一种相关性良好的预测生物活性的神经网络模型,模型的总相关系数R_(t)为0.942.预测的活性值与其实验值(p EC_(50))的相对平均误差仅为1.26%.利用该神经网络模型设计了10种新的活性大的4-羟氨基-α-吡喃酮甲酰胺类似物分子,并计算得到活性预测值.结果表明,4-羟氨基-α-吡喃酮甲酰胺类似物生物活性与价键指数、电性距离矢量具有良好的非线性关系.Formamide is an important pharmaceutical chemical intermediate and an important component of many bioactive compounds.It is widely used in pharmaceutical,pesticide and other productive industries.In order to study the quantitative structure-activity relationship(QSAR)between the activity of 4-hydroxyamino-α-pyranone carboxamide analogues and their mo-lecular structure,a novel molecular structure index-valence bond index B was derived based on characteristics and connectivity of the atoms in molecules.Moreover,the electrical distance vectors of 424-hydroxyamino-α-pyranone carboxamide analogues were calculated,and the electrical distance vectors M_(14),M_(77) and M_(78) were taken as theoretical structure descriptors.Electrical distance vectors were combined with valence bond index B,and they were introduced to the regression analysis of the activity of 4-hydroxyamino-α-pyranone carboxamide analogues.Using the four molecular parameters as input layer parameters of the neural network,and 4-4-1 as network structure,a predictive model with good correlation was con-structed to predict biological activity.The total correlation coefficient R_(t) was 0.942.The average rel-ative error between the experimental value and the predicted values(p EC_(50))was only 1.26%.Ac-cording to the radar chart of relative of prediction values,it can be seen that the distribution of relative errors is relatively uniform,and there is no abnormal error value that deviates from the circular area,which indicates that the predicted results of the activity of formamide analogues obtained by the model are in good agreement with the experimental values.Ten novel 4-hydroxyamino-α-pyranone carbox-amide analogues with high activity were designed by using the neural network model,and predicted values of activity were calculated.The result showed that there is a good non-linear relationship be-tween the valence bond index,electrical distance vectors and the biological activity of 4-hydroxyami-no-α-pyranone carboxamide analogues.

关 键 词：4-羟氨基-α-吡喃酮甲酰胺类似物 价键指数 电性距离矢量 神经网络法 定量结构-活性关系 

分 类 号：O641[理学—物理化学]