Synthesis and serotonin transporter activity of 1,3-bis(aryl)-2-nitro-1-propenes as a new class of anticancer agents
Publication: Research - peer-review › Journal 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-review › Journal article – Annual report year: 2011
Harvard
APA
CBE
MLA
Vancouver
Author
Bibtex
}
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
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
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
M3 - Journal article
VL - 19
SP - 1328
EP - 1348
JO - Bioorganic & Medicinal Chemistry
T2 - Bioorganic & Medicinal Chemistry
JF - Bioorganic & Medicinal Chemistry
SN - 0968-0896
IS - 3
ER -