物理化学学报 >> 2014, Vol. 30 >> Issue (6): 1086-1090.doi: 10.3866/PKU.WHXB201404161

理论与计算化学 上一篇    下一篇

多种类杂环化合物的药理和毒理活性系数构效关系

朱志臣1, 王强2, 贾青竹3, 夏淑倩4, 马沛生4   

  1. 1 天津城建大学理学院, 天津300384;
    2 天津科技大学材料科学与化学工程学院, 天津300457;
    3 天津科技大学海洋科学与工程学院, 天津300457;
    4 天津大学化工学院, 天津300072
  • 收稿日期:2014-01-14 修回日期:2014-04-16 发布日期:2014-05-26
  • 通讯作者: 王强 E-mail:wang_q@tust.edu.cn
  • 基金资助:

    国家自然科学基金(21306137,U1162104)资助项目

Structure-Property Relationship for the Pharmacological and Toxicological Activity of Heterocyclic Compounds

ZHU Zhi-Chen1, WANG Qiang2, JIA Qing-Zhu3, XIA Shu-Qian4, MA Pei-Sheng4   

  1. 1 School of Science, Tianjin University of Urban Construction, Tianjin 300384, P. R. China;
    2 School of Material Science and Chemical Engineering, Tianjin University of Science and Technology, Tianjin 300457, P. R. China;
    3 School of Marine Science and Engineering, Tianjin University of Science and Technology, Tianjin 300457, P. R. China;
    4 School of Chemical Engineering and Technology, Tianjin University, Tianjin 300072, P. R. China
  • Received:2014-01-14 Revised:2014-04-16 Published:2014-05-26
  • Contact: WANG Qiang E-mail:wang_q@tust.edu.cn
  • Supported by:

    The project was supported by the National Natural Science Foundation of China (21306137, U1162104).

摘要:

杂环类化合物在卫生保健和药物分子设计领域发挥关键作用,在西药中占有重要地位. 本工作针对扩展距离矩阵提出了一组范数指数,基于扩展距离矩阵的范数指数构建了一个新的构效关系模型,并对杂环类化合物二苯并呋喃的芳烃受体亲和性(pEC50)以及芳香和杂环芳香胺的诱导有机体变异力(lnR)进行了计算预测.结果表明,基于扩展距离矩阵范数指数建立的构效关系模型可以很好地预测pEC50和lnR. 其中,pEC50预测结果的平均绝对误差(AAD)为0.403,相关性系数r2=0.876,lnR预测结果的AAD为0.702,r2=0.779. 与其他预测方法的对比结果表明,本工作不仅能够利用一个完全相同的数学表达模型同时对pEC50和lnR进行预测,而且预测结果在准确性和稳定性上都有显著改善.

关键词: 二苯并呋喃, 芳香和杂环芳香胺, 芳烃受体亲和性, 诱导有机体变异力, 构效关系, 范数指数, 预测

Abstract:

Heterocyclic molecules play a crucial role in health care and in pharmaceutical drug design. A large number of drugs used in Western medical practice are heterocyclic molecules. In this study, a set of norm indexes of the extended distance matrix are proposed. From these a stable and accurate structureproperty relationship model was developed for the prediction of the aryl hydrocarbon receptor binding affinity (pEC50) of dibenzofurans and the mutagenic potency (lnR) of aromatic and heteroaromatic amines. Our results indicate that the new model, based on these norm indexes, provides very satisfactory results, and that the average absolute differences for pEC50 prediction and lnR prediction were 0.403 and 0.702 with r2 (square correlation coefficient) values of 0.876 and 0.779, respectively. A comparison of these results with other methods demonstrates that our method, based only on the same mathematical model, performed better in terms of both accuracy and stability.

Key words: Dibenzofuran, Aromatic and heteroaromatic amine, Aryl hydrocarbon receptor affinity, Mutagenic potency, Structure-property relationship, Norm index, Prediction

MSC2000: 

  • O641