新型香豆素类衍生物的合成及抗肿瘤活性研究

Synthesis and Anticancer Activity of Novel Coumarin Derivatives

为了寻找结构新颖、活性较好的抗肿瘤化合物,设计合成了19个未见文献报道的3,4,5-三甲氧基苯基香豆素类化合物,并用核磁共振(NMR)和高分辨质谱(HRMS)等方法对化合物结构进行表征.用四甲基偶氮唑盐(MTT)法评价了该类化合物对人前列腺癌细胞(PC-3)、人食管癌细胞(EC-109)和人胃癌细胞(MGC-803)三种肿瘤细胞的抑制活性.结果显示,N-苄基-2-((4-甲基-2H-色烯-2-酮-7-基)氧基)-N-(3,4,5-三甲氧基苯基)乙酰胺(4a)和N-((5-氯苯并[b]噻吩-3-基)甲基)-2-((4-甲基-2H-色烯-2-酮-7-基)氧基)-N-(3,4,5-三甲氧基苯基)乙酰胺(4n)对三种肿瘤细胞的抑制活性优于阳性对照药5-氟尿嘧啶,其中化合物4n对人前列腺癌细胞(PC-3)的抑制活性最好,其IC(50)为4.18μmol/L.

Nineteen novel 3,4,5-trimethoxyphenyl coumarin derivatives have been synthesized and evaluated for antitumor activity against three human cancer cell lines(EC-109,PC-3 and MGC-803).These chemical structures were well characterized by NMR and HRMS spectroscopic methods.N-Benzyl-2-((4-methyl-2-oxo-2H-chromen-7-yl)oxy)-N-(3,4,5-trimethoxy-phenyl)acetamide(4a)and N-((5-chlorobenzo[b]thiophen-3-yl)methyl)-2-((4-methyl-2-oxo-2H-chromen-7-yl)oxy)-N-(3,4,5-trimethoxyphenyl)acetamide(4n)had better inhibitory activity against three kinds of tumor cells than 5-fluorouracil.Compound 4n showed the most potent antitumor activity against PC-3 cells with an IC50 value of 4.18μmol/L.