去甲去氢斑蝥素衍生物的合成及细胞毒活性  

Synthesis and Cytotoxicity Activity of Dehydronorcantharidin Derivatives

作　　者：张建强[1] 徐阳荣 孟庆国[1] ZHANG Jian-qiang XU Yang-rong MENG Qing-guo(School of Pharmacy, Key Laboratory of Molecular Pharmacology and Drug Evaluation, Ministry of Education, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shan Dong, Yantai University, Yantai, 264005, Chin)

机构地区：[1]烟台大学新型制剂与生物技术药物研究山东省高校协同创新中心分子药理和药物评价教育部重点实验室,山东烟台264005

出　　处：《烟台大学学报（自然科学与工程版）》2016年第4期265-270,共6页Journal of Yantai University(Natural Science and Engineering Edition)

基　　金：山东省自然科学基金资助项目(ZR2012HM036)

摘　　要：以顺丁烯二酸酐和呋喃为起始原料,经Diels-Alder缩合、取代和缩合3步反应,合成了14个新的去甲去氢斑蝥素衍生物2a^2g和3a^3g以及6个羧酸钠盐4a,4c^4g,其中2a^2g和3a^3g结构均经ESI-MS和1H NMR确证.用MTT法初步测定2a^2g和3a^3g对人肝癌细胞SMMC-7721和人肺癌细胞A549的体外细胞毒活性,结果表明,2e和3a的细胞毒活性优于去甲去氢斑蝥素.用MTT法初步检测了4a、4c^4g对A549增殖的影响,发现其对A549的抑制作用均弱于去甲去氢斑蝥素.Fourteen novel dehydronorcantharidin derivatives 2a -2g, 3a -3g and six novel carboxylic acid sodium salt derivatives 4a, 4c - 4g have been synthesized through Diels - Alder [ 4 ＋ 2 ] condensation, substitution and condensation from furan and maleic anhydride. The structures of 2a -2g, 3a -3g are confirmed by ESI-MS and 1H NMR. The cytotoxic activities in vitro of 2a- 2g, 3a-3g against SMMC-7721 and A549 are investigated by MTT assay, and the result shows that 2e and 3a possess significant cytotoxic activitiy in contract to dehydronorcantharidin. The preliminary proliferation inhibition activities of 4a, 4c -4g against A549 are tested by MTr assay, and it is found that their inhibition activities are weaker than dehydronorcantharidin.

关 键 词：去甲去氢斑蝥素 衍生物 合成 细胞毒活性 

分 类 号：R914.5[医药卫生—药物化学]