摘要
为了研究阱基单胺氧化酶抑制剂(Hydrazinyl monoamine oxygenase inhibitor,HMAOI)的抑制活性(pI50)的定量构效关系(Quantitative structure-activity relationship,QSAR),按照分子的拓扑环境编程计算了22种HMAOI的电性距离矢量(mk)。利用最佳变量子集回归,建立了它们的3参数(m6、m9、m33)QSAR模型,非交叉验证与交叉验证的相关系数R2和Q2分别为0.957、0.914,具有良好的稳健性和预测能力。该模型显示,影响HMAOI抑制活性的主要因素是—CH3,—CH<,—NH—,—O—及羰基等分子结构单元。以此三个参数为人工神经网络输入层,设定3∶4∶1的网络结构,构建人工神经网络的BP算法模型,传统相关系数R为0.997,标准偏差S为0.035。结果表明,HMAOI的pI50与m6、m9、m33呈良好的非线性关系,用其表征pI50具有合理性和有效性,为设计高抑制活性的HMAOI提供理论依据。
In order to study the quantitative structure-activity relationship （QSAR）of the inhibited activity （P/s0） for hydrazinyl monoamine oxygenase inhibitor （ HMAOI）, the molecular electronegativity distance vector（mk ）of 22 HMAOI is calculated by program according to the molecular topological en- vironment in this paper. The three-parameter （ m6, m9 and m33 ） QSAR model of plso for 22 HMAOI is constructed by leaps-and-bounds regression（LBR）. The traditional correlation coefficient （R2） and the cross-validation correlation coefficient（ Q2 ） are 0.957 and 0. 914, respectively. The result demonstrates that the model is highly reliable and has good predictive ability from the point of view of statistics. The three parameters of the model show that the dominant influencing factors of inhibited activity are the molecular structure fragments：--CH3 ,--CH 〈,--NH--,--O-- and carbonyl in HMAOI. The three structural parameters are used as the input neurons of artificial neural network, and a 3：4：1 network architecture is employed. A satisfied model can be constructed with the back-propagation algorithm, the correlation coefficient R and the standard error（s）are 0. 997 and 0. 035, respectively. This shows that the relationship between plso and three structural parameters is a good nonlinear correlation. The results show that the parameter m6, m9 and m33 have good rationality and efficiency for the plso of hydrazinyl monoamine oxygenase. The model can provide some theoretical insights into the design of this series of HMAOI with higher inhibited activity.
出处
《南京理工大学学报》
EI
CAS
CSCD
北大核心
2012年第4期711-716,共6页
Journal of Nanjing University of Science and Technology
基金
国家自然科学基金(21075138)
徐州市科技局基金(XZZD1104)
贾汪科技局基金(XM10A05)
关键词
计算化学
阱基单胺氧化酶抑制剂
抑制活性
电性距离矢量
定量构效关系
computational chemistry
hydrazinyl monoamine oxygenase
inhibited activity
electronegativity distance vector
quantitative structure-activity relationship
作者简介
冯长君（1954-），男，教授，主要研究方向：物质构效学，E-mail：fengejxznu@jsnu．edu．cn。
