靛玉红类衍生物电子结构与抗癌活性关系的研究

Relationship between Electronic Structure and Antitumor Activity of Indirubin Derivatives

目的:研究靛玉红类衍生物电子结构与抗癌活性的构效关系。方法:采用CNDO/2分子轨道法计算靛玉红类衍生物分子的电子结构,应用分子力学方法计算分子的构象,并结合相关分析和逐步回归分析方法探讨其构效关系。结果:靛玉红类衍生物分子中4号氧原子的净电荷Q4、3号C原子的净电荷Q3与其抗癌活性显著相关,并得到与Q4的定量构效关系:Iw=-40.03-246.96×Q4。当分子的键角L1为125°-132°,扭转角L2为11°-12°时,分子活性构象能够与靶标的活性部位更好地结合。结论:靛玉红类衍生物分子构象中有两个活性点(即药效基团),这两个活性点提供电子给靶标的活性部位。而有利于它们之间结合的构象,都可使其相互间的结合力提高,从而使抗癌活性增加。

Objective: To investigate the relationship between the structure and the activity of indirubin derivatives. Methods: By using the quantum chemical CNDO/2 method and the molecular mechanics method,the QSAR and active sites of indirubin derivatives were discussed. Results: The net charges of Q3 at position 3 and Q4 at position 4 were greatly related to the antitumor activity. The quantitative structure activity relationship was established as Iw=-40.03-246.96×Q4. While the molecular rotating angle L1 were 125°-132° and L2 were 11°-12°, the antitumor activity was increased. Conclusions: The antitumor activity of the indirubin derivatives can be predicated by QSAR. The oxygen 4 and carbon 3 are important active sites of the indirubin derivatives.