3-羧基香豆素衍生物的合成和抗肿瘤活性

Synthesis and Antitumor Activity of Coumarin-3-carboxylic Derivatives

以取代水杨醛和丙二酸二乙酯为原料,经缩合、取代和水解等反应,设计合成了10个新的3-羧基香豆素衍生物,采用1HNMR、13CNMR和HR-MS对合成的化合物结构进行了表征,并利用MTS法考察了其对人肝癌细胞HepG2、结肠癌细胞HCT116及正常肝细胞L-02的抗增殖活性。结果表明,7-环戊氧基-3-羧基香豆素、7-环己氧基-3-羧基香豆素和7-苄氧基-3-羧基香豆素对HepG2细胞的抗增殖活性最强(IC50分别为5.02、2.94、3.65μmol/L),而7-异丁氧基-3-羧基香豆素和7-苯乙氧基-3-羧基香豆素对HCT116细胞的活性最强,其IC50分别为5.14、9.63μmol/L。对HepG2细胞活性最好的化合物7-环己氧基-3-羧基香豆素与顺铂(cis-DDP)联用的结果显示,该化合物能显著增强顺铂对HepG2细胞的抗增殖作用。这些研究结果可为香豆素类抗肿瘤先导化合物的研究开发提供科学依据。

Ten new coumarin-3-carboxylic derivatives were designed and synthesized from substituted salicylaldehydes and diethyl malonate via condensation,substitution and hydrolyzation reactions.Their structures were characterized by 1HNMR,13CNMR and HR-MS.The antiproliferative activity of these compounds against human liver cancer cell line HepG2,colon cancer cell line HCT116 and human normal liver cell line L-02 was evaluated by MTS method in vitro.The results showed that 7-cyclopentoxy-3-carboxyl coumarin,7-cyclohexoxy-3-carboxyl coumarin and 7-benzyloxy-3-carboxyl coumarin had the best antiproliferative activity against HepG2 cell,their IC50 values were 5.02,2.94 and 3.65 μmol/L,respectively.Additionally,7-isobutyloxy-3-carboxyl coumarin and 7-phenethoxy-3-carboxyl coumarin also had potent activity against HCT116 cell with the corresponding IC50 values of 5.14 and 9.63 μmol/L.The results of the combination of the most potent 7-cyclohexoxy-3-carboxyl coumarin and cis-DDP showed that this compound significantly enhanced the antiproliferation effect of cis-DDP against HepG2 cell.The results may provide a scientific evidence for the further research and development of antitumor coumarin lead compounds.