1,4-二氢吡啶衍生物的QSAR模型构建及制备  

QSAR model construction and synthesis of 1,4-dihydropyridine derivatives

作　　者：刘媛媛 李玲 陈学军 李壹[2] LIU Yuan-yuan;LI Ling;CHEN Xue-jun;LI Yi(College of Pharmaceutical and Chemical Engineering,Southeast University Chengxian College,Nanjing 210088,China;College of Food Science and Light Industry,Nanjing Tech University,Nanjing 211816,China)

机构地区：[1]东南大学成贤学院制药与化学工程学院,江苏南京210088 [2]南京工业大学食品与轻工学院,江苏南京211816

出　　处：《化学研究与应用》2023年第3期515-524,共10页Chemical Research and Application

基　　金：江苏省自然科学基金面上项目(BK20211001)资助;江苏省青蓝工程中青年学术带头人(2021)资助;东南大学成贤学院青年教师科研发展基金项目(z0033)资助;南京工业大学高性能计算中心计算支持。

摘　　要：采用Hyperchem 8.0软件,通过分子动力学MM+和半经验AM1算法,优化并计算得到30种1,4-二氢吡啶衍生物的17种量子化学参数。运用Statistica 8.0软件中的主成分分析法,结合线性回归分析法,筛选出3个最佳参数与1,4-二氢吡啶衍生物的抗结核活性关联,构建定量构效关系(QSAR)模型。所建多元线性回归方程的相关系数R2为0.75,留一法交叉检验系数q2为0.72,活性实验值与预测值相关性较好。采用该模型设计并制备得到1种具有良好水溶性和潜在抗结核活性的N3,N5-二(对磺酸钾基)苯基-2,6-二甲基-3,5-二甲酰氨基-1,4-二氢吡啶(TM),用1H NMR、IR、MS和元素分析表征结构,并考察了紫外和荧光性能。良好的稳定性和预测能力使该QSAR模型有望用于结核病候选药物的筛选。Molecular dynamics MM+method and semiempirical AM1 method in Hyperchem 8.0 software were used to optimize and calculate seventeen quantum chemical parameters of thirty 1,4-dihydropyridine derivatives.The optimal parameters were screened by principal component analysis method and regression analysis method in Statistica 8.0 software.The anti-tuberculosis activities of these compounds with three optimal parameters were used to establish the quantitative structure-activity relationships(QSAR)model.The statistical results indicated that the correlation coefficients R 2 and q 2 in the multiple linear regression and cross-validation using Leave-One-Out method were 0.75 and 0.72,respectively.The predicted values were in good agreement with the observed activities.Based on this model,compound potassium 4,4′-((2,6-dimethyl-1,4-dihydropyridine-3,5-dicarbonyl)bis(azanediyl))dibenzenesulfonate(TM)with good water solubility and potential anti-tuberculosis activity was designed,prepared and characterized by 1H NMR,IR,MS and elemental analysis.Its UV and fluorescence properties were also investigated.Good stability and predictive ability make the QSAR model possible for screening tuberculosis candidate drugs.

关 键 词：1 4-二氢吡啶衍生物 抗结核活性 定量构效模型 量子化学参数 紫外和荧光性能 

分 类 号：O651[理学—分析化学]