摘要
基于化学拓扑理论,计算了20种硫色烯并噻唑胺类衍生物分子的电性距离矢量指数(m_t)。经最佳变量子集回归方法建立上述分子对电鳗乙酰胆碱酯酶体外抑制活性(pM)与m_t的最佳三元QSAR模型,其判定系数(R^2)和逐一剔除法交叉验证系数R_(cv)~2依次为0.936和0.850。通过R^2、R_(adj)~2、F、R_(cv)~2、V_(IF)、A_(IC)、F_(IT)等检验,该模型具有令人满意的稳健性和预测能力。依据模型分析硫色烯并噻唑胺类衍生物对电鳗乙酰胆碱酯酶体外抑制的可能机理,其中,氢键起到主要及正向作用,分子疏水性则起次要且为负向作用。
The molecular electronegativity distance vector （mt） was used to describe the chemical structures of 20 kinds of N-acyl-thiochromenothiazol-2-amine derivatives. The optimal variable subset regression method was adopted to establish the three element model between inhibition activities of above molecules to acetylcholinesterase of electric eel and m,. The correlation coefficients （R2） and leave-one-out （LOO） cross validation Rcv2 of the optimal three-parameter QSAR models were 0. 936 and 0. 850 for pM model, respectively. The QSAR model has both favorable robustness and good prediction capability by R2, Radj2, F, Roy2, VIF, AIC, FIT tests. The possible mechanism for the inhibition of acetylcholinesterase has been proposed according to the model. On the basis of the model analysis, hydrogen bond plays a primary and positive role, however, hydrophobicity plays the secondary and negative one.
作者
冯惠
王志荣
冯长君
Feng Hui Wang Zhirong Feng Changjun(School of Chemistry ＆ Chemical Engineering, Xuzhou Institute of Technology, Xuzhou 221111 Department of Cardiology, the Affiliated Hospital of Xuzhou Medical University, Xuzhou, 221002)
出处
《化学通报》
CAS
CSCD
北大核心
2017年第2期191-195,共5页
Chemistry
基金
国家自然科学基金项目(21075138)
结构化学国家重点实验室开放基金项目(2016003)
徐州工程学院科研项目(XKY2012307
XKY2013103)资助
关键词
硫色烯并噻唑胺类衍生物
电性距离矢量
电鳗乙酰胆碱酯酶
体外抑制活性
抑制机理定量构效关系
N-acyl-thiochromenothiazol-2-amine derivative, Molecular electronegativity distance vector, Acetylcholinesterase of electric eel, Inhibition activity, Inhibition mechanism, Quantitative structure-activity relationship
