黄酮类化合物与γ-氨基丁酸A型受体相互作用的定量构效关系建模

QSAR modeling of the interaction of flavonoids with GABA(A) receptor.

作者信息

Duchowicz Pablo R, Vitale Martín G, Castro Eduardo A, Autino Juan C, Romanelli Gustavo P, Bennardi Daniel O

机构信息

Research Institute of Theoretical and Applied Physical Chemistry (INIFTA), Theoretical Chemistry Division, Chemistry Department, La Plata National University, Diag. 113 y 64, Suc. 4, C.C. 16, La Plata 1900, Argentina.

出版信息

Eur J Med Chem. 2008 Aug;43(8):1593-602. doi: 10.1016/j.ejmech.2007.11.009. Epub 2007 Nov 22.

DOI:10.1016/j.ejmech.2007.11.009

PMID:18158201

Abstract

Experimentally assigned values to binding affinity constants of flavonoid ligands towards the benzodiazepine site of the GABA(A) receptor complex were compiled from several publications, and enabled to perform a predictive analysis based on Quantitative Structure-Activity Relationships (QSAR). The best linear model established on 78 molecular structures incorporated four molecular descriptors, selected from more than a thousand of geometrical, topological, quantum-mechanical and electronic types of descriptors and calculated by Dragon software. An application of this QSAR equation was performed by estimating the binding affinities for some newly synthesized flavonoids displaying 2-,7-substitutions in the benzopyrane backbone which still do not have experimentally measured potencies.

摘要

从多篇出版物中收集了黄酮类配体与GABA(A)受体复合物苯二氮䓬位点结合亲和力常数的实验赋值，并基于定量构效关系（QSAR）进行了预测分析。在78个分子结构上建立的最佳线性模型纳入了四个分子描述符，这些描述符是从一千多种几何、拓扑、量子力学和电子类型的描述符中挑选出来的，并通过Dragon软件计算得出。通过估算一些新合成的在苯并吡喃主链上具有2,7-取代基且尚无实验测定效力的黄酮类化合物的结合亲和力，应用了该QSAR方程。