基于密度泛函理论的萜类化合物促进药物经人体皮肤吸收的定量构效关系模型研究  

Establishment of the Quantitative Structure-Activity Relationship between the Structure of Terpenoids and Their Enhancing Drug Penetration Ability through Human Skin Based on Density Functional Theory

作　　者：龚明星[1] 谢茵[1] 宋舒琴 唐海飞[1] 张玲玲[1] 钟华[1] 田青平[1] 

机构地区：[1]山西医科大学药学院,太原030001

出　　处：《中国药学杂志》2015年第15期1324-1329,共6页Chinese Pharmaceutical Journal

基　　金：山西省自然科学基金资助项目(2012011007-5);山西省科技攻关资助项目(20140313018-8)

摘　　要：目的主要以表征分子"反应活性"的结构参数为自变量,建立预测其经皮促渗活性的定量构效关系模型(QSAR)。方法采用DFT中的B3/LYP方法 ,在6-311++G(2d,p)基组上,对41种萜类化合物进行结构优化,计算其结构参数和热力学参数,用逐步线性回归中的后退法建立预测萜类化合物促进药物经人体皮肤吸收的定量构效关系模型。结果得到复相关系数(r2)为0.655,交互检验系数的平方RCV2为0.654。模型表明,表面静电势(VS,ta,VS,max,VS,min)、化学势(λ)、热容(Cp)、偶极矩(D)与萜类化合物的离体经皮促渗活性间具有良好的线性相关性。结论由密度泛函量子化学理论获得的反应活性指标可更好地模拟促渗剂结构与其经皮促渗活性间的相关性,有利于定量构效关系模型的合理解释。OBJECTIVE To establish the quantitative structure-activity relationship （QSAR） for predicting the percutaneous permeation enhancing activity of terpenoids, using the indexes of reactivity in molecules as the important descriptors. METHODS The structural and thermodynamic parameters of 41 terpenoids were optimized using B3/LYP method of DFT at the level of 6-311 ＋ ＋ G （2d,p）. The backward method in stepwise multiple regression was used to establish the QSAR model for predicting activities of ter- penes that enhanced drug penetration through human skin. RESULTS The multiple correlation coefficient （ r2 ） was determined to be 0. 655 and the square cross validated correlation coefficient （Rcv2） was determined to be 0. 654. The QSAR model indicated that the e- lectrostatic potentials （Vs Vs Vs,m~~ ）, chemical potential （k）, thermal capacity （Cp）, and dipole moment （D） of individual molecules could be responsible for the in vitro permeation enhancing abilities of terpenoids. CONCLUSION The indexes of reactivity in molecules based on density functional theory can simulate more exactly the quantitative relationship between the structures of penetration enhancers and their percutaneous permeation enhancing abilities for drugs, which will facilitate reasonable explanation of the model.

关 键 词：结构参数 热力学参数 渗透活性 定量构效关系模型方程 密度泛函 

分 类 号：R944[医药卫生—药剂学]