7-羟基-香豆素-3-羧酸衍生物的合成及抗肿瘤活性  

Synthesis and anticancer activity of 7-hydroxy-coumarin-3-carboxylic acid derivatives

作　　者：顾宏霞 何冰[1] 谭鸿舟 严志奇 何黎琴 吴虹 GU Hong-xia;HE Bing;TAN Hong-zhou;YAN Zhi-qi;HE Li-qin;WU Hong(China College of Pharmacy,Anhui University of Chinese Medicine,Hefei 230012,China;West Anhui Health Vocational College,Luan 237000,China)

机构地区：[1]安徽中医药大学药学院,安徽合肥230012 [2]皖西卫生职业学院,安徽六安237000

出　　处：《化学研究与应用》2023年第11期2711-2717,共7页Chemical Research and Application

基　　金：安徽省教育厅自然科学科研项目(KJ2020A0957,KJ2021B003)资助。

摘　　要：以2,4-二羟基苯甲醛和丙二酸二乙酯为起始原料,经Knoevenagel反应得到7-羟基-香豆素-3-羧酸乙酯(2);再经曼尼希反应、酯水解、酸化,得到7-羟基-8-氨甲基-香豆素-3羧酸(4a~4e);利用其羧基与不同碳数的二溴烷烃反应得到相应的溴代酯(5a~5i),再与硝酸银反应得到9个有机硝酸酯类一氧化氮(NO)供体型7-羟基-香豆素-3羧酸衍生物(6a~6i)。目标化合物的结构经过核磁共振氢谱、碳谱和高分辨质谱确证。用MTT法评价了目标化合物对人肝癌HepG2细胞和人肺癌A549细胞增殖的影响,结果显示,所合成的目标化合物对受试的两种癌细胞均具有较强的增殖抑制作用,其中,化合物6c的活性最好。Using 2,4-dihydroxybenzaldehyde and diethyl malonate as starting materials,7-hydroxy-8-aminomethyl-coumarin-3-car-boxylic acid(4a~4e)were synthesized via Knoevenagel reaction,Mannich reaction,ester hydrolysis and acidification.Compound 4 was treated with Br(CH,),Br(n=2~6)in the presence of K,CO,to provide the compounds 7-hydroxy-8-aminomethyl-coumarin-3-carboxylic acid bromoalkyl ester(5a~5i),these compounds were then reacted with silver nitrate to give the target compounds 7-hy-droxy-coumarin-3-carboxylic acid derivatives(6a~6i).Their chemical structure was confirmed by^(1)H NMR,^(13)C NMR and HRMS.The antitumor activity of these derivatives was evaluated against two human tumor cell lines(A549 and HepG2).All of the synthe-sized compounds exhibited good activity against the tested cell lines.Particularly,compound 6c exhibited more potent antiprolifera-tive activity against the tested tumor cell lines.

关 键 词：7-羟基-香豆素-3-羧酸 曼尼希碱 硝酸酯 NO供体 抗肿瘤活性 

分 类 号：O623.62[理学—有机化学]