期刊文献+

2-芳基苯并噁唑衍生物的三维定量构效关系研究

Three dimensional quantitative structure-activity relationship of 2-arylbenzoxazole derivatives
原文传递
导出
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
  • 相关文献

参考文献2

二级参考文献27

  • 1李翀,何昌荣,王琛,赵红芬.粗粒料大型三轴试验的尺寸效应研究[J].岩土力学,2008(S01):563-566. 被引量:45
  • 2陈生水.土石坝试验新技术研究与应用[J].岩土工程学报,2015,37(1):1-28. 被引量:31
  • 3王继庄.粗粒料的变形特性和缩尺效应[J].岩土工程学报,1994,16(4):89-95. 被引量:73
  • 4Bonham L, Leung DW, White T, et al. Lysophosphatidic acid acyltransferase-beta : a novel target for induction of tumour cell apoptosis. Expert Opin Ther Targets, 2003 ;7:643 - 661
  • 5Coon M, Ball A, Pound J, et al. Inhibition of lysophosphatidic acid acyhransferase beta disrupts proliferative and survival signals in normal cells and induces apoptosis of tumor cells. Mol Cancer Ther, 2003 ;2 : 1067 - 1078
  • 6Tang W, Yuan J, Chen X, et al. Identification of a novel human lysophosphatidic acid acyltransferase, LPAAT-theta, which activates mTOR pathway. J Biochem Mol Biol, 2006 ;39:626 - 635
  • 7Agarwal AK, Arioglu E, De-Almeida S, et al, AGPAT2 is mutated in congenital generalized lipodystrophy linked to chromosome 9q34. Nat Genet, 2002;31:21 -23
  • 8Niesporek S, Denkert C, Weichert W, et al. Expression of lysophosphatidic acid acyltransferase beta (LPAAT-beta) in ovarian carcinoma: correlation with tumour grading and prognosis. Br J Cancer. 2005 ;92 : 1729 - 1736
  • 9Leung DW. The structure and functions of human lysophosphatidic acid acyltransferases. Front Biosci. 2001 ;6:D944 -953
  • 10Diefenbach CS, Soslow RA, Iasonos A, et al. Lysophosphatidic acid acyltransferase-beta (LPAAT-beta) is highly expressed in advanced ovarian cancer and is associated with aggressive histology and poor survival. Cancer, 2006 ; 107 : 1511 - 1159

共引文献12

相关作者

内容加载中请稍等...

相关机构

内容加载中请稍等...

相关主题

内容加载中请稍等...

浏览历史

内容加载中请稍等...
;
使用帮助 返回顶部