鱼藤素断环结构氨基酸衍生物的合成及其抗肿瘤活性

摘要

采用化学法,以异戊烯醛和2,4-二羟基苯甲醛为起始原料,经烯醛加成和醛胺缩合反应合成了4种新的鱼藤素断环结构氨基酸衍生物(3a~3d),其结构经1H NMR, 13C NMR和LC-MS表征.采用CCK8法将3a~3d作用于H1299肺癌细胞和HBE正常细胞,对其抗肿瘤活性和毒性进行初步研究.结果表明:3a~3d对肺癌H1299细胞增殖表现出不同程度的抑制作用,均呈现时间浓度依赖性.与鱼藤素相比,3a~3d的抗肿瘤活性下降, 3d的活性最好,IC50为655.8±34.7μmol·L-1,但对HBE正常肺细胞的毒性明显小于鱼藤素.%Four novel ring-truncated deguelin-amino acid conjugates(3a~3d) were synthesized by olefine aldehyde addition and aldimine condensation from 3-methylcrotonaldehyde and 2,4-dihydroxybenzaldehyde.The structures were characterized by 1H NMR, 13C NMR and LC-MS.The anticancer effects and toxicities were investigated by CCK8 method.The results showed that 3a~3d exhibited good inhibition activities and time dose dependence.Although compared with deguelin, antitumor activities of 3a~3d declined, IC50 of 3d which has the best activity was 655.8±34.7 μmol·L-1, however their toxicity towards immortalized HBE lung cell were also settled.