冬凌草甲素衍生物的合成及其抗肿瘤活性研究  

Study on Synthesis and Anti-tumor Activity of Oridonin Derivatives

作　　者：杨宏静[1] 方应权[1] 沈庆坤 尚凡凡 全哲山[2] 张训浩[1] YANG Hong-jing;FANG Ying-quan;SHEN Qing-kun;SHANG Fan-fan;QUAN Zhe-shan;ZHANG Xun-hao(School of Pharmacy,Chongqing Three Gorges Medical College,Chongqing 404120,China;School of Pharmacy,Yanbian University,Yanji 133002,China)

机构地区：[1]重庆三峡医药高等专科学校药学院,重庆404120 [2]延边大学药学院,吉林延吉133002

出　　处：《化学试剂》2021年第2期147-151,共5页Chemical Reagents

基　　金：校级重大自然科学课题地方特色药材活性成分提取及抗肿瘤研究项目(2018zdxz01)。

摘　　要：以冬凌草甲素为原料,丁二酸为连接臂在其C-14位引入氨基磷酸酯及含氮化合物,设计并合成了6个未见文献报道的目标化合物。所有衍生物均经过氢谱、碳谱以及高分辨质谱进行结构确认,并采用噻唑蓝比色法(MTT)对目标化合物进行人结肠癌HCT-116、人肝癌BEL-7402、人乳腺癌MCF-7细胞系抗癌活性筛选。结果表明,绝大多数化合物表现出较强的抗增殖作用,其中(1S,4aR,5S,6S,6aR,9S,11aS,11bS,14R)-1,5,6-三羟基-4,4-二甲基-8-亚甲基-7-氧代十二氢-1H-6,11b-(环氧甲酰基)-6a,9-甲基环庚[a]萘-14-基4-(((二乙氧基磷酰基)(苯基)甲基)氨基)-4-氧代丁酸酯表现出最强的抗增殖作用,尤其对人乳腺癌MCF-7细胞系的抗增殖活性最好,其IC_(50)值仅为2.73μmol/L,活性提高约4.61倍,具有进一步开发的价值。Six unreported compounds were designed and synthesized by using oridonin as raw material,and introducing aminophosphate and nitrogenous compounds into the C-14 position of succinic acid as the connecting arm.The structures of all derivatives were confirmed by HNMR,CNMR and high resolution mass spectrometry,and the anticancer activities of human colon cancer HCT-116,human liver cancer BEL-7402 and human breast cancer MCF-7 cell lines were screened by MTT assay.The most of the compounds showed strong anti-proliferative effect,among which(1S,4aR,5S,6S,6aR,9S,11aS,11bS,14R)-1,5,6-trihydroxy-4,4-dimethyl-8-methylene-7-oxododecahydro-1H-6,11b-(epoxymethano)-6a,9-methanocyclohepta[a]naphthalene-14-yl 4-(((diethoxyphosphoryl)(phenyl) methyl) amino)-4-oxobutanoate showed the strongest anti-proliferative effect,especially for human colon cancer MCF-7 cell line,the anti-proliferative activity was the best,its IC_(50) value was only 2.73 μmol/L,the activity was increased by about 4.61 times,and it had the value of further development.

关 键 词：冬凌草甲素 合成 抗肿瘤 氨基磷酸酯 

分 类 号：R914.5[医药卫生—药物化学]