鱼藤素断环结构氨基酸衍生物的合成及其抗肿瘤活性

Synthesis and Antitumor Activities of Ring-truncated Deguelin-amino Acid Conjugates

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,^(13)C 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,IC_(50)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 o- lefine aldehyde addition and aldimine condensation from 3-methylcrotonaldehyde and 2,4-dihydroxy- benzaldehyde. 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 ac- tivities of3a ~3d declined, IC50 of 3d which has the best activity was 655.8 ±34.7 μmol · L-1, how- ever their toxicity towards immortalized HBE lung cell were also settled.