新型亲脂性 N-取代去甲斑蝥素衍生物的合成及抗癌活性评价。
Synthesis of novel lipophilic N-substituted norcantharimide derivatives and evaluation of their anticancer activities.
机构信息
Department of Microbiology, Immunology and Biopharmaceutics, College of Life Sciences, National Chiayi University, Chiayi 60004, Taiwan.
Laboratory of Biophysics, Department of Medical Research, Taipei Veterans General Hospital, Taipei 11217, Taiwan.
出版信息
Molecules. 2014 May 26;19(6):6911-28. doi: 10.3390/molecules19066911.
This research attempted to study the effect of lipophilicity on the anticancer activity of N-substituted norcantharimide derivatives. Twenty-three compounds were synthesized and their cytotoxicities against five human cancer cell lines studied. The lipophilicity of each derivative was altered by its substituent, an alkyl, alkyloxy, terpenyl or terpenyloxy group at the N-position of norcantharimide. Further, among all synthesized derivatives studied, the compounds N-farnesyloxy-7-oxabicyclo[2.2.1]heptane-2,3-dicarboximide (9), and N-farnesyl-7-oxabicyclo[2.2.1]heptane-2,3-dicarboximide (18), have shown the highest cytotoxicity, anti-proliferative and apoptotic effect against human liver carcinoma HepG2 cell lines, yet displayed no significant cytotoxic effect on normal murine embryonic liver BNL CL.2 cells. Their overall performance led us to believe that these two compounds might be potential candidates for anticancer drugs development.
本研究试图研究脂溶性对 N-取代降琥胺衍生物抗癌活性的影响。合成了 23 种化合物，并研究了它们对五种人癌细胞系的细胞毒性。通过在降琥胺的 N-位引入烷基、烷氧基、萜烯基或萜烯氧基取代基来改变每个衍生物的脂溶性。此外，在所研究的所有合成衍生物中，化合物 N-法呢基氧基-7-氧杂双环[2.2.1]庚烷-2,3-二羧酸亚胺（9）和 N-法呢基-7-氧杂双环[2.2.1]庚烷-2,3-二羧酸亚胺（18）对人肝癌 HepG2 细胞系表现出最高的细胞毒性、抗增殖和凋亡作用，但对正常鼠胚胎肝 BNL CL.2 细胞没有显著的细胞毒性作用。它们的综合表现使我们相信，这两种化合物可能是抗癌药物开发的潜在候选物。
Zotero 插件