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

作　　者：孙婧雯[1,2] 姜志辉[2] 吴碧娟[2] 谭翠雯 吴新荣[1,2] 

机构地区：[1]华南理工大学食品科学与工程学院,广东广州510641 [2]广州军区广州总医院药学部,广东广州510010

出　　处：《合成化学》2017年第4期291-296,共6页Chinese Journal of Synthetic Chemistry

基　　金：广东省科技计划项目(2011A080300004);广州市科技计划项目(201509010012)

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,^(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.

关 键 词：异戊烯醛 2 4-二羟基苯甲醛 鱼藤素 氨基酸衍生物 合成 抗肿瘤活性 

分 类 号：O621.3[理学—有机化学] O629.71[理学—化学]