Synthesis and serotonin transporter activity of 1,3-bis(aryl)-2-nitro-1-propenes as a new class of anticancer agents

Publication: Research - peer-reviewJournal article – Annual report year: 2011

  • Author: McNamara, Yvonne M.

    Trinity College Dublin, School of Pharmacy and Pharmaceutical Sciences

  • Author: Cloonan, Suzanne M.

    Trinity College Dublin, School of Biochemistry and Immunology

  • Author: Knox, Andrew J.S.

    Trinity College Dublin, School of Biochemistry and Immunology

  • Author: Keating, John J.

    Trinity College Dublin, School of Pharmacy and Pharmaceutical Sciences

  • Author: Butler, Stephen G.

    Trinity College Dublin, School of Pharmacy and Pharmaceutical Sciences

  • Author: Peters, Günther H.J.

    Physical Chemistry, Department of Chemistry, Technical University of Denmark, Denmark

  • Author: Meegan, Mary J.

    Trinity College Dublin, School of Pharmacy and Pharmaceutical Sciences

  • Author: Williams, D. Clive

    Trinity College Dublin, School of Biochemistry and Immunology

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Structural derivatives of 4-MTA, an illegal amphetamine analogue have been previously shown to have anticancer effects in vitro. In this study we report the synthesis of a series of novel 1,3-bis(aryl)-2-nitro-1-propene derivatives related in structure to 4-MTA. A number of these compounds containing a classic nitrostyrene structure are shown to have antiproliferative activities in vitro in a range of malignant cell lines, particularly against Burkitt’s lymphoma derived cell lines, whilst having no effect on ‘normal’ peripheral blood mononuclear cells. Such effects appear to be independent of the serotonin transporter, a high affinity target for amphetamines and independent of protein tyrosine phosphatases and tubulin dynamics both of which have been previously associated with nitrostyrene-induced cell death. We demonstrate that a number of these compounds induce caspase activation, PARP cleavage, chromatin condensation and membrane blebbing in a Burkitt’s lymphoma derived cell line, consistent with these compounds inducing apoptosis in vitro. Although no specific target has yet been identified for the action of these compounds, the cell death elicited is potent, selective and worthy of further investigation.
Original languageEnglish
JournalBioorganic & Medicinal Chemistry
Publication date2011
Volume19
Issue3
Pages1328-1348
ISSN0968-0896
DOIs
StatePublished
CitationsWeb of Science® Times Cited: 4

Keywords

  • Apoptosis, Nitrostyrene, Serotonin transporter (SERT), 4-Methylthioamphetamine (4-MTA), Burkitt’s lymphoma, Cancer, Programmed cell death
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