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

Standard

Synthesis and serotonin transporter activity of 1,3-bis(aryl)-2-nitro-1-propenes as a new class of anticancer agents. / McNamara, Yvonne M.; Cloonan, Suzanne M.; Knox, Andrew J.S.; Keating, John J.; Butler, Stephen G.; Peters, Günther H.J.; Meegan, Mary J.; Williams, D. Clive.

In: Bioorganic & Medicinal Chemistry, Vol. 19, No. 3, 2011, p. 1328-1348.

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

Harvard

McNamara, YM, Cloonan, SM, Knox, AJS, Keating, JJ, Butler, SG, Peters, GHJ, Meegan, MJ & Williams, DC 2011, 'Synthesis and serotonin transporter activity of 1,3-bis(aryl)-2-nitro-1-propenes as a new class of anticancer agents' Bioorganic & Medicinal Chemistry, vol 19, no. 3, pp. 1328-1348., 10.1016/j.bmc.2010.11.054

APA

McNamara, Y. M., Cloonan, S. M., Knox, A. J. S., Keating, J. J., Butler, S. G., Peters, G. H. J., ... Williams, D. C. (2011). Synthesis and serotonin transporter activity of 1,3-bis(aryl)-2-nitro-1-propenes as a new class of anticancer agents. Bioorganic & Medicinal Chemistry, 19(3), 1328-1348. 10.1016/j.bmc.2010.11.054

CBE

McNamara YM, Cloonan SM, Knox AJS, Keating JJ, Butler SG, Peters GHJ, Meegan MJ, Williams DC. 2011. Synthesis and serotonin transporter activity of 1,3-bis(aryl)-2-nitro-1-propenes as a new class of anticancer agents. Bioorganic & Medicinal Chemistry. 19(3):1328-1348. Available from: 10.1016/j.bmc.2010.11.054

MLA

Vancouver

Author

McNamara, Yvonne M.; Cloonan, Suzanne M.; Knox, Andrew J.S.; Keating, John J.; Butler, Stephen G.; Peters, Günther H.J.; Meegan, Mary J.; Williams, D. Clive / Synthesis and serotonin transporter activity of 1,3-bis(aryl)-2-nitro-1-propenes as a new class of anticancer agents.

In: Bioorganic & Medicinal Chemistry, Vol. 19, No. 3, 2011, p. 1328-1348.

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

Bibtex

@article{cb547a17e90b4b818553846b5c600d5d,
title = "Synthesis and serotonin transporter activity of 1,3-bis(aryl)-2-nitro-1-propenes as a new class of anticancer agents",
keywords = "Apoptosis, Nitrostyrene, Serotonin transporter (SERT), 4-Methylthioamphetamine (4-MTA), Burkitt’s lymphoma, Cancer, Programmed cell death",
publisher = "Pergamon",
author = "McNamara, {Yvonne M.} and Cloonan, {Suzanne M.} and Knox, {Andrew J.S.} and Keating, {John J.} and Butler, {Stephen G.} and Peters, {Günther H.J.} and Meegan, {Mary J.} and Williams, {D. Clive}",
year = "2011",
doi = "10.1016/j.bmc.2010.11.054",
volume = "19",
number = "3",
pages = "1328--1348",
journal = "Bioorganic & Medicinal Chemistry",
issn = "0968-0896",

}

RIS

TY - JOUR

T1 - Synthesis and serotonin transporter activity of 1,3-bis(aryl)-2-nitro-1-propenes as a new class of anticancer agents

A1 - McNamara,Yvonne M.

A1 - Cloonan,Suzanne M.

A1 - Knox,Andrew J.S.

A1 - Keating,John J.

A1 - Butler,Stephen G.

A1 - Peters,Günther H.J.

A1 - Meegan,Mary J.

A1 - Williams,D. Clive

AU - McNamara,Yvonne M.

AU - Cloonan,Suzanne M.

AU - Knox,Andrew J.S.

AU - Keating,John J.

AU - Butler,Stephen G.

AU - Peters,Günther H.J.

AU - Meegan,Mary J.

AU - Williams,D. Clive

PB - Pergamon

PY - 2011

Y1 - 2011

N2 - 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.

AB - 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.

KW - Apoptosis

KW - Nitrostyrene

KW - Serotonin transporter (SERT)

KW - 4-Methylthioamphetamine (4-MTA)

KW - Burkitt’s lymphoma

KW - Cancer

KW - Programmed cell death

U2 - 10.1016/j.bmc.2010.11.054

DO - 10.1016/j.bmc.2010.11.054

JO - Bioorganic & Medicinal Chemistry

JF - Bioorganic & Medicinal Chemistry

SN - 0968-0896

IS - 3

VL - 19

SP - 1328

EP - 1348

ER -