天然黄酮Mannich碱衍生物的合成及生物活性研究

摘要

Two naturally occurring flavones,apigenin-5,4′-dimethy ether(1) and lutedin-5,3′,4′-trimethyl ether(2),were synthesized through I2/Py dehydrogenation,O-methylation and glycoside hydrolysis reaction,using naringin and hesperidin as raw materials. Based on Mannich reaction of flavones 1 or 2 with various secondary amines and formaldehyde in acidic alcohol solvent with microwave assisted,fifteen novel flavones Mannich base derivatives 1-17 were synthesized. The structures of all synthesized compounds were confirmed by 1H NMR,13C NMR and MS techniques. Furthermore,all compounds were tested for anti-proliferative activities on human cervical carcinoma Hela cells using cell counting Kit-8(CCK-8). The results showed that compounds 1,2,7, 9,10,12 and 17 exhibited distinct anti-proliferative activities against Hela cells. Among them,compounds 10,12 and 17 displayed higher activities with inhibitory concentration 50%(IC50) of 16.13, 29.04 and 9.14 μmol/L than the positive control cis-platin (IC50 =41. 25 μmol/L).%以柚皮苷和橙皮苷为原料,经碘/吡啶脱氢,O-甲基化和糖苷水解等反应,分别合成了2种天然黄酮芹菜素-5,4′-二甲醚(1)和木犀草素-5,3′,4′-三甲醚(2)。然后以1和2为底物,分别与甲醛、二级胺在酸性醇溶剂中发生微波协助的Mannich反应,对黄酮8-位进行胺甲基化修饰,合成了15个新型黄酮Mannich碱衍生物3~17。所合成的化合物经1H NMR、13C NMR和MS等进行了结构确证,并采用细胞计数Kit-8(CCK-8)法测试了化合物1~17对子宫颈癌Hela细胞的体外抑制活性。结果表明,化合物1、2、7、9、10、12和17对Hela细胞增殖具有明显的抑制活性,其中化合物10、12和17的半数抑制浓度( IC50)分别为16.13、29.04和9.14μmol/L,活性高于阳性对照药物顺铂(IC50为41.25μmol/L)。