[1]冯长君.喹唑啉衍生物抗胃癌活性的CoMFA模型[J].徐州工程学院学报(自然科学版),2022,(1):31-35.
 FENG Changjun.CoMFA Model of Anti-gastric Cancer Activity of Quinazoline Derivatives[J].Journal of Xuzhou Institute of Technology(Natural Sciences Edition),2022,(1):31-35.
点击复制

喹唑啉衍生物抗胃癌活性的CoMFA模型()
分享到:

《徐州工程学院学报》(自然科学版)[ISSN:1674-358X/CN:32-1789/N]

卷:
期数:
2022年第1期
页码:
31-35
栏目:
化学工程
出版日期:
2022-03-30

文章信息/Info

Title:
CoMFA Model of Anti-gastric Cancer Activity of Quinazoline Derivatives
文章编号:
1674-358X(2022)01-0031-05
作者:
冯长君
(徐州工程学院 材料与化学工程学院,江苏 徐州 221018)
Author(s):
FENG Changjun
(School of Material & Chemical Engineering, Xuzhou University of Technology, Xuzhou 221018, China)
关键词:
喹唑啉衍生物 抗胃癌活性 比较分子力场分析 分子设计
Keywords:
quinazoline derivative anti-gastric cancer activity comparative molecular field analysis molecular design
分类号:
X171.5; O6-051
文献标志码:
A
摘要:
基于比较分子力场分析(CoMFA)方法建立23种喹唑啉衍生物抗胃癌活性(pMG)的三维定量构效关系(3D-QSAR).训练集中20个化合物用于建立预测模型,测试集6个化合物(含16号模板分子及2个新设计的分子)作为模型验证.建立的CoMFA模型的交叉验证系数(Q2)、非交叉验证系数(R2)分别为0.312、0.854,说明所建模型具有较强的稳定性和良好的预测能力.该模型中立体场、静电场贡献率依次为62.6%、37.4%,表明影响抗胃癌活性(pMG)的主要因素是取代基的疏水性和空间位阻,其次是取代基的库仑力、氢键及配位.基于该研究结果,设计了2个具有较高抗胃癌活性的新化合物.
Abstract:
Based on the comparative molecular field analysis(CoMFA)method, three dimensional quantitative structure-activity relationships(3D-QSAR)between the molecular structures and their anti-gastric cancer activity(pMG)of 23 quinazoline derivatives were established. Twenty compounds in the training set were served to build the predicting models, and the six compounds(containing template molecule 16 and newly designed two molecules)in the test set were used to validate the models. The coefficients of the cross-validation(Q2)and non-cross-validation(R2)for CoMFA model established in this study are 0.312 and 0.854, respectively. The results show that the model has strong stability and good predictability. In this model, the contributions of the steric and electrostatic fields were 62.6% and 37.4%, respectively, indicating that the main factors to impact on pMG are the hydrophobic factor and steric hindrance of substituted groups, followed by Coulomb force, hydrogen bonds and coordination of substituted groups. Based on the results of this study, two new compounds with high anti-gastric cancer activity were designed.

参考文献/References:

[1] 刘海彬,李增强.4-氨基喹唑啉类衍生物的合成及体外抗肿瘤活性[J].合成化学,2021,29(9):782-785.
[2] 张成路,暴金迪,于丰铭,等.以喹唑啉酮为核心高选择高灵敏识别次氯酸根离子的荧光探针的合成及应用[J].应用化学,2021,38(8):986-994.
[3] 王婷,梁艳妮,刘建利,等.4-苯胺喹唑啉类化合物合成研究进展[J].化学通报,2021,84(7):680-689.
[4] 汪正捷,戴洪林,司晓杰,等.含三氟甲基的 2,4,6-三取代喹唑啉衍生物的合成及抗肿瘤活性研究[J/OL].有机化学,2022,42(1):249-256.
[5] 冯长君.取代三唑-噻二唑类化合物生物活性的QSAR研究[J].徐州工程学院学报(自然科学版),2018,33(4):39-44.
[6] 冯长君.物质构效学应用[M].徐州:中国矿业大学出版社,2017:13-15.
[7] WANG C,FENG C J.QSAR studies on the inhibitory activity of levofloxacin-thiadiazole HDACi conjugates to histone deacetylases[J].Chinese Journal of Structural Chemistry,2018,37(11):1679-1688.
[8] WANG J L,LI L,HU M B,et al.In silico drug design of inhibitor of nuclear factor kappa b kinase subunit beta inhibitors from 2-acylamino-3-aminothienopyridines based on quantitative structure-activity relationships and molecular docking[J].Computational Biology and Chemistry,2019,78(1):297-305.
[9] 冯长君.苯磺酰脲类化合物除草活性的CoMFA模型[J].徐州工程学院学报(自然科学版),2019,34(2):21-25.
[10] TONG J B,WANG Y,LEI S,et al.3D-QSAR and docking studies of 1,3,4-thiazolidinone derivatives using R-group search and surflex-dock[J].Chinese Journal of Structural Chemistry,2019,38,464-475.
[11] 冯长君.硝基苯衍生物对发光菌抑制毒性的CoMFA模型[J].徐州工程学院(自然科学版),2020,35(1):28-31.
[12] FENG H,DU X H,CHEN Y,et al.3D-QSAR models of anti-tumor activity for histone deacetylase inhibitors containing dihydropyridin-2-one[J].Chinese Journal of Structural Chemistry,2020,39(5):855-862.
[13] FENG H,FENG C J.3D-QSAR studies on the anti-tumor activity of N-Aryl-salicylamide derivatives[J].Chinese Journal of Structural Chemistry,2019,38(11):1874-1880.
[14] 唐自强,冯惠,冯长君.噻吩并嘧啶衍生物抗胃癌活性的CoMFA模型与分子设计[J].原子与分子物理学报,2021,38(3):1-6.
[15] 胡松青,米思奇,贾晓林,等.苯并咪唑类缓蚀剂的3D-QSAR研究及分子设计[J].高等学校化学学报,2011,32(10):2402-2409.
[16] 张骥,申鹏,陆涛,等.黄酮类化合物抑制MMP-9的定量结构-活性关系和结构修饰的理论研究[J].化学学报,2011,69(4):383-392.
(责任编辑 崔思荣)

备注/Memo

备注/Memo:
收稿日期:2021-10-29
基金项目: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(2016028)
作者简介:冯长君(1954—),男,教授,主要从事药物构效关系研究.
更新日期/Last Update: 2022-03-30