title: Synthesis and antiproliferative action of a novel series of maprotiline analogues.
abstract: The synthesis of a diverse library of compounds structurally related to maprotiline, a norepinephrine reuptake transporter (NET) selective antidepressant which has recently been identified as a novel in vitro antiproliferative agent against Burkitt's lymphoma (BL) cell lines is reported. A series of 9,10-dihydro-9,10-ethanoanthracenes were synthesised with modifications to the bridge of the dihydroethanoanthracene structure and with alterations to the basic side chain. A number of compounds were found to reduce cell viability to a greater extent than maprotiline in BL cell lines. In addition a related series of novel 9-substituted anthracene compounds were investigated as intermediates in the synthesis of 9,10-dihydro-9,10-ethanoanthracenes. These compounds proved the most active from the screen and were found to exert a potent caspase-dependant apoptotic effect in the BL cell lines, while having minimal effect on the viability of peripheral blood mononuclear cells (PBMCs). Compounds also displayed activity in multi-drug resistant (MDR) cells.
authors: School of Pharmacy & Pharmaceutical Sciences, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin, Ireland.
authors: Y M
authors: YM
authors: McNamara
authors: School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin, Ireland. Electronic address: brights@tcd.ie.
authors: S A
authors: SA
authors: Bright
authors: School of Pharmacy & Pharmaceutical Sciences, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin, Ireland.
authors: A J
authors: AJ
authors: Byrne
authors: School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin, Ireland.
authors: S M
authors: SM
authors: Cloonan
authors: School of Chemistry, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin, Ireland.
authors: T
authors: T
authors: McCabe
authors: School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin, Ireland.
authors: D C
authors: DC
authors: Williams
authors: School of Pharmacy & Pharmaceutical Sciences, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin, Ireland.
authors: M J
authors: MJ
authors: Meegan
mesh_terms: D018759:Adrenergic Uptake Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002051:Burkitt Lymphoma / Q000188:drug therapy*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000187:drug effects; D008376:Maprotiline / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000494:pharmacology*; D050486:Serotonin Plasma Membrane Transport Proteins
chemical_list: D018759:Adrenergic Uptake Inhibitors; D000970:Antineoplastic Agents; D050486:Serotonin Plasma Membrane Transport Proteins; D008376:Maprotiline
keywords: Burkitt's lymphoma; Ethanoanthracenes; Maprotiline; Multidrug resistance