摘要
应用Cerius2软件中的主成分分析法(PCA)和Var.Jarvis-Patrick聚类方法对新型含噻唑和三唑环的亚胺类杂环化合物进行分类,再用遗传函数算法(GFA)和分子力场分析方法(MFA)分别进行了二维/三维定量构效关系研究(QSAR),所建模型都通过了显著性检验,CV-r2均大于0.910,表明模型都具有良好的预测可靠性。计算研究表明:分子的热力学性质(各种原子类型A logP描述符)、空间结构状态(Jurs参数和Shadow参数)和电拓扑状态指数(S_aaCH)是影响活性的主要二维因素。三维研究结果表明,分子的静电作用强弱对活性影响较大。最后根据药物分子设计理论设计了一系列亚胺类化合物,并用所建最优二维/三维QSAR模型进行活性预测与相互验证,筛选出活性可能较高的6个化合物。该研究可为高效亚胺类杀菌剂的研制提供理论指导。
A series of novel imine heterocyclic compounds containing thiazole and triazole ring were classified by Var. Jarvis-Patrick clustering method coupled with principal component analysis （PCA） and then the quantitative structure-activity relationships （QSAR） were investigated using genetic function approximation （GFA） and molecular field analysis （MFA）, respectively. All models were cross-validated with CV-P over 0. 910 and used to predict the compounds with reported activity. The results demonstrate that all models are significant with good stability and predictability. The 2D-results indicated that molecular thermodynamic properties （ atom type AlogP descriptors）, steric states （ Jurs and Shadow parameters） and electrotopological state indice （S_aaCH） contribute to the activity. The steric function is mostly involved in activity demonstrated by 3D-study. A series of imine compounds were designed according to the theory of drug design and their activity was predicted and reciprocally validated using optimized 2/3D-QSAR models. Six compounds with potential high activity were finally screened. In conclusion, the results in the research are valuable for designing novel effective imine fungicides.
出处
《农药学学报》
CAS
CSCD
2008年第3期268-274,共7页
Chinese Journal of Pesticide Science
基金
国家自然科学基金资助项目(30500339)
浙江省自然科学基金资助项目(Y407308)
关键词
亚胺类杀菌剂
遗传函数算法
分子力场分析
定量构效关系
分子设计
imine fungicides
genetic function approximation （GFA）
molecular field analysis （MFA）
quantitative structure-activity relationships （QSAR）
molecular design
