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Eur J Med Chem. 2014 Jan;71:333-53. doi: 10.1016/j.ejmech.2013.10.076. Epub 2013 Nov 9.

Synthesis and antiproliferative action of a novel series of maprotiline analogues.

Author information

1
School of Pharmacy & Pharmaceutical Sciences, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin, Ireland.
2
School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin, Ireland. Electronic address: brights@tcd.ie.
3
School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin, Ireland.
4
School of Chemistry, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin, Ireland.

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.

KEYWORDS:

Burkitt's lymphoma; Ethanoanthracenes; Maprotiline; Multidrug resistance

PMID:
24333581
DOI:
10.1016/j.ejmech.2013.10.076
[Indexed for MEDLINE]

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