摘要
溶血磷脂酸酰基转移酶-β(LPAAT-β)是肿瘤治疗的新靶点,2-芳基苯并噁唑衍生物是最近发现的LPAAT-β抑制剂,可以选择性抑制LPAAT-β的活性,从而抑制肿瘤细胞的增殖。本文运用比较分子力场分析(CoMFA)建立了2-芳基苯并噁唑LPAAT-β抑制剂的三维定量构效关系(3D-QSAR)模型,考察了网格步长对模型的影响。优化后的模型交叉验证系数q^2=0.626,最佳主成分数为3,传统的相关系数r^2=0.933,统计方差比F=102.391。该模型对训练集和测试集化合物进行预测,预测值和实验值非常接近,表明模型具有很好的预测能力。该模型显示立体场和静电场对生物活性的贡献分别为59.5%和40.5%。CoMFA模型的三维等值图可为改造化合物结构提供理论依据。
Lysophosphatidic acid acyltransferase-β(LPAAT-β) is a novel target for cancer therapy.A group of 2-arylbenzoxazole compounds have been reported as LPAAT-βinhibitors,which can selectively inhibit the functions of LPAAT-β,and then inhibit the proliferation of tumor cells.The three dimensional quantitative structure-activity relationship has been studied on these 2-arylbenzoxazole LPAAT-βinhibitors by comparative molecular field analysis(CoMFA).Variation of grid space was used during the optimization of the CoMFA model.The optimized CoMFA model had a cross validated coefficient q^2 of 0.626 with an optimized component of 3,non-cross validated coefficient r^2 of 0.933,and its F value is 102.391.The activity of test and training compounds predicted by this model was agreed with the experimental results.The statistic parameters of the model show that the model is predictive.The contributions of steric and electrostatic fields to the activity are 59.5%and 40.5%,respectively.The CoMFA model gives the basis on the structure modification of 2-arylbenzoxazole LPAAT-βinhibitors.
出处
《计算机与应用化学》
CAS
CSCD
北大核心
2010年第4期439-442,共4页
Computers and Applied Chemistry
基金
广州市粤港关键领域重点突破项目(2006z1-E6021)
关键词
三维定量构效关系
比较分子力场分析
2-芳基苯并噁唑
LPAAT-β抑制剂
three dimensional quantitative structure activity relationship(3D-QSAR)
comparative molecular field analysis(CoMFA)
2-arylbenzoxazole
LPAAT-βinhibitor