title: Synthesis of novel lipophilic N-substituted norcantharimide derivatives and evaluation of their anticancer activities.
abstract: 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.
authors.affiliation: Department of Microbiology, Immunology and Biopharmaceutics, College of Life Sciences, National Chiayi University, Chiayi 60004, Taiwan. jywu@mail.ncyu.edu.tw.
authors.forename: Jin-Yi
authors.initials: JY
authors.lastname: Wu
authors.affiliation: Laboratory of Biophysics, Department of Medical Research, Taipei Veterans General Hospital, Taipei 11217, Taiwan.
authors.forename: Cheng-Deng
authors.initials: CD
authors.lastname: Kuo
authors.affiliation: Department of Microbiology, Immunology and Biopharmaceutics, College of Life Sciences, National Chiayi University, Chiayi 60004, Taiwan.
authors.forename: Chien-Yu
authors.initials: CY
authors.lastname: Chu
authors.affiliation: Department of Microbiology, Immunology and Biopharmaceutics, College of Life Sciences, National Chiayi University, Chiayi 60004, Taiwan.
authors.forename: Min-Shin
authors.initials: MS
authors.lastname: Chen
authors.affiliation: Department of Microbiology, Immunology and Biopharmaceutics, College of Life Sciences, National Chiayi University, Chiayi 60004, Taiwan.
authors.forename: Jia-Hua
authors.initials: JH
authors.lastname: Lin
authors.affiliation: Department of Radiation Oncology, Mackay Memorial Hospital, New Taipei City 25160, Taiwan.
authors.forename: Yu-Jen
authors.initials: YJ
authors.lastname: Chen
authors.affiliation: Department of Biochemical Science and Technology, College of Life Sciences, National Chiayi University, Chiayi 60004, Taiwan.
authors.forename: Hui-Fen
authors.initials: HF
authors.lastname: Liao
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000737:chemistry*; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D056945:Hep G2 Cells; D006801:Humans; D051379:Mice
chemical_list: D000970:Antineoplastic Agents; D019086:Bridged Bicyclo Compounds, Heterocyclic; C069741:norcantharidin