Synthesis of Novel Lipophilic N-Substituted Norcantharimide Derivatives and Evaluation of Their Anticancer Activities

Molecules

Jin-Yi Wu²  Cheng-Deng Kuo¹  Chien-Yu Chu²  Min-Shin Chen²  Jia-Hua Lin²  Yu-Jen Chen³ 

[1] Laboratory of Biophysics, Department of Medical Research, Taipei Veterans General Hospital, Taipei 11217, Taiwan;Department of Microbiology, Immunology and Biopharmaceutics, College of Life Sciences, National Chiayi University, Chiayi 60004, Taiwan;Department of Radiation Oncology, Mackay Memorial Hospital, New Taipei City 25160, Taiwan

关键词: norcantharimide derivatives;    lipophilic substitution;    terpenyl group;    anticancer activity;    HepG2;    apoptosis;   

DOI  :  10.3390/molecules19066911

来源: mdpi

【 摘 要 】

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.

【 授权许可】

CC BY   
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