多靶点受体酪氨酸激酶抑制剂喹啉衍生物的合成及活性初步研究

发布时间：2018-05-27 06:01

  本文选题：喹啉衍生物 + 多靶点　； 参考：《中国新药杂志》2016年13期

【摘要】：目的:合成一系列喹啉苯甲酰胺类衍生物(3a~3l,4a~4h)作为多靶点受体酪氨酸激酶抑制剂,并进行体外抗肿瘤活性研究。方法:以4,7-二氯喹啉和对氨基苯甲酸为起始原料,经2步或3步反应合成目标化合物。采用四氮唑盐(MTT)法测试目标化合物对A549,Eca-109,Hela这3种肿瘤细胞的抑制作用。结果:所合成的化合物中抑制活性最强为化合物4a,对Hela,Eca-109及A549细胞的IC50值分别为(1.04±0.12),(0.37±0.06),(2.16±1.05)μmol·L~(-1),对肿瘤细胞的抑制活性强于舒尼替尼(sunitinib)。结论:与舒尼替尼相比,本实验中所涉及到化合物均表现出一定的抑制活性,这类喹啉苯甲酰胺类衍生物能够作为多靶点受体酪氨酸激酶抑制剂进行深入研究。
[Abstract]:Aim: to synthesize a series of quinoline benzoyl amines as multitarget receptor tyrosine kinase inhibitors and to study their antitumor activity in vitro. Methods: the target compound was synthesized by two or three steps reaction of 4-4-dichloroquinoline and p-aminobenzoic acid. The inhibitory effects of the target compounds on A549 Eca-109 Hela tumor cells were measured by MTT method. Results: the inhibitory activity of the synthesized compounds was the strongest for 4 years, and the IC50 values of the two compounds were 1.04 卤0.12, 0.37 卤0.06 渭 mol / L, respectively, and the inhibitory activity on tumor cells was stronger than that on susunitinib. Conclusion: compared with sulnitinib, the compounds involved in this study have some inhibitory activities, and these quinoline benzoyl amines can be used as multi-target receptor tyrosine kinase inhibitors.
【作者单位】： 华侨大学分子药物研究院;广州优米健医药科技有限公司;
【基金】：福建省自然科学基金资助项目(2015J01342) 泉州市科技计划重点项目(Z1424024)
【分类号】：R914.5
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本文编号：1940730