吡啶类葡萄糖激酶激动剂的三维定量构效关系分析
发布时间：2018-11-15 17:24
【摘要】：葡萄糖激酶GK是调节体内葡萄糖代谢和参与血糖动态平衡的主要靶点之一。本文针对46个具有GK激动剂活性的吡啶类衍生化合物进行构效关系研究,研究了其结构与活性的关系。基于分子共同骨架叠合用分子力场分析法(COMFA),比较分子相似指数法(COMSIA)两种经典三维定量构效关系(3D-QSAR)方法,建立相应模型,进行分子结构和抗糖尿病活性分析。COMFA模型的交叉验证系数q~2为0.613,相关系数r~2为0.989;COMSIA模型交叉验证系数q~2为0.621,相关系数r~2为0.982。数据证明两种模型都显示出较好的预测性,为设计新的活性更高的小分子激动剂提供了可靠信息。
[Abstract]:Glucokinase GK is one of the main targets to regulate glucose metabolism and to participate in the homeostasis of blood glucose. The structure-activity relationships of 46 pyridine derivatives with GK agonist activity were studied. Based on the comparison of molecular similarity index method (COMSIA) and three dimensional quantitative structure-activity relationship (3D-QSAR) method by molecular force field analysis (COMFA), the corresponding model was established based on the molecular common skeleton superposition. The molecular structure and antidiabetic activity were analyzed. The cross validation coefficient of COMFA model was 0.613, and the correlation coefficient was 0.989; The cross validation coefficient of COMSIA model was 0. 621, and the correlation coefficient was 0. 982. The data show that both models show good predictability and provide reliable information for the design of new and more active small molecular agonists.
【作者单位】： 重庆理工大学药学与生物工程学院;
【基金】：国家自然科学基金项目(31170747,81171508资助 重庆市自然科学基金项目(cstc2015jcyjBX0080)资助 重庆市教委科技项目(KJ1600907)资助
【分类号】：R914
本文编号：2333958
[Abstract]:Glucokinase GK is one of the main targets to regulate glucose metabolism and to participate in the homeostasis of blood glucose. The structure-activity relationships of 46 pyridine derivatives with GK agonist activity were studied. Based on the comparison of molecular similarity index method (COMSIA) and three dimensional quantitative structure-activity relationship (3D-QSAR) method by molecular force field analysis (COMFA), the corresponding model was established based on the molecular common skeleton superposition. The molecular structure and antidiabetic activity were analyzed. The cross validation coefficient of COMFA model was 0.613, and the correlation coefficient was 0.989; The cross validation coefficient of COMSIA model was 0. 621, and the correlation coefficient was 0. 982. The data show that both models show good predictability and provide reliable information for the design of new and more active small molecular agonists.
【作者单位】： 重庆理工大学药学与生物工程学院;
【基金】：国家自然科学基金项目(31170747,81171508资助 重庆市自然科学基金项目(cstc2015jcyjBX0080)资助 重庆市教委科技项目(KJ1600907)资助
【分类号】：R914
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