Redesigning the designer drug ecstasy: non-psychoactive MDMA analogues exhibiting Burkitt's lymphoma cytotoxicity
Identifieur interne : 001B24 ( Main/Exploration ); précédent : 001B23; suivant : 001B25Redesigning the designer drug ecstasy: non-psychoactive MDMA analogues exhibiting Burkitt's lymphoma cytotoxicity
Auteurs : Michael N. Gandy [Australie] ; Matthew Mcildowie [Australie] ; Katie Lewis [Australie] ; Agata M. Wasik [Royaume-Uni] ; Danielle Salomonczyk [Canada] ; Keith Wagg [Australie] ; Zak A. Millar [Australie] ; David Tindiglia [Australie] ; Philippe Huot [Canada] ; Tom Johnston [Canada] ; Sherri Thiele [Canada] ; Blake Nguyen [Australie] ; Nicholas M. Barnes [Royaume-Uni] ; Jonathan M. Brotchie [Canada] ; Mathew T. Martin-Iverson [Australie] ; Joanne Nash [Canada] ; John Gordon [Royaume-Uni] ; Matthew J. Piggott [Australie]Source :
- MedChemComm [ 2040-2503 ] ; 2010.
Abstract
Burkitt's lymphoma (BL) is a particularly aggressive cancer that primarily affects African children. Unfortunately, effective and affordable treatment is out of reach of most of the afflicted. The illicit psychoactive drug methylenedioxymethamphetamine (MDMA, ecstasy) is cytotoxic to BL cell lines, but its low potency, psychoactivity and neurotoxicity preclude consideration as a therapeutic drug candidate. This paper describes the discovery of novel -aryl analogues of MDMA that lack psychoactivity and reduce BL cell line viability with significantly more potency than the lead compound. Preliminary in vitro studies also indicate that the compounds are non-toxic to a relevant neuronal cell line.
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DOI: 10.1039/c0md00108b
Affiliations:
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Barnes</name><affiliation wicri:level="4"><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Clinical and Experimental Medicine, The Medical School, University of Birmingham, B15 2TT</wicri:regionArea><orgName type="university">Université de Birmingham</orgName><placeName><settlement type="city">Birmingham</settlement><region type="country">Angleterre</region><region type="région" nuts="1">Midlands de l'Ouest</region></placeName></affiliation></author><author wicri:is="90%"><name sortKey="Brotchie, Jonathan M" sort="Brotchie, Jonathan M" uniqKey="Brotchie J" first="Jonathan M." last="Brotchie">Jonathan M. Brotchie</name><affiliation wicri:level="1"><country xml:lang="fr">Canada</country><wicri:regionArea>Toronto Western Research Institute, Toronto Western Hospital, M5T 2S8, 399 Bathurst Street, MC 11-419, ON, Toronto</wicri:regionArea><wicri:noRegion>Toronto</wicri:noRegion></affiliation></author><author wicri:is="90%"><name sortKey="Martin Iverson, Mathew T" sort="Martin Iverson, Mathew T" uniqKey="Martin Iverson M" first="Mathew T." last="Martin-Iverson">Mathew T. Martin-Iverson</name><affiliation wicri:level="1"><country xml:lang="fr">Australie</country><wicri:regionArea>School of Medicine and Pharmacology, The University of Western Australia, 6009, WA, Crawley</wicri:regionArea><wicri:noRegion>Crawley</wicri:noRegion></affiliation></author><author wicri:is="90%"><name sortKey="Nash, Joanne" sort="Nash, Joanne" uniqKey="Nash J" first="Joanne" last="Nash">Joanne Nash</name><affiliation wicri:level="1"><country xml:lang="fr">Canada</country><wicri:regionArea>Centre for Neurobiology of Stress, Department of Biological Sciences, University of Toronto at Scarborough, M1C 1A4, 1265 Military Trail, ON, Toronto</wicri:regionArea><wicri:noRegion>Toronto</wicri:noRegion></affiliation></author><author wicri:is="90%"><name sortKey="Gordon, John" sort="Gordon, John" uniqKey="Gordon J" first="John" last="Gordon">John Gordon</name><affiliation wicri:level="4"><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>MRC Centre for Immune Regulation, The Medical School, University of Birmingham, B15 2TT</wicri:regionArea><orgName type="university">Université de Birmingham</orgName><placeName><settlement type="city">Birmingham</settlement><region type="country">Angleterre</region><region type="région" nuts="1">Midlands de l'Ouest</region></placeName></affiliation></author><author wicri:is="90%"><name sortKey="Piggott, Matthew J" sort="Piggott, Matthew J" uniqKey="Piggott M" first="Matthew J." last="Piggott">Matthew J. Piggott</name><affiliation wicri:level="1"><country xml:lang="fr">Australie</country><wicri:regionArea>School of Biomedical, Biomolecular and Chemical Sciences, The University of Western Australia, 6009, WA, Crawley</wicri:regionArea><wicri:noRegion>Crawley</wicri:noRegion></affiliation><affiliation wicri:level="1"><country wicri:rule="url">Australie</country></affiliation></author></analytic><monogr></monogr><series><title level="j">MedChemComm</title><title level="j" type="abbrev">Med. Chem. Commun.</title><idno type="ISSN">2040-2503</idno><idno type="eISSN">2040-2511</idno><imprint><publisher>The Royal Society of Chemistry.</publisher><date type="published" when="2010">2010</date><biblScope unit="volume">1</biblScope><biblScope unit="issue">4</biblScope><biblScope unit="page" from="287">287</biblScope><biblScope unit="page" to="293">293</biblScope></imprint><idno type="ISSN">2040-2503</idno></series></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">2040-2503</idno></seriesStmt></fileDesc><profileDesc><textClass></textClass><langUsage><language ident="en">en</language></langUsage></profileDesc></teiHeader><front><div type="abstract">Burkitt's lymphoma (BL) is a particularly aggressive cancer that primarily affects African children. Unfortunately, effective and affordable treatment is out of reach of most of the afflicted. The illicit psychoactive drug methylenedioxymethamphetamine (MDMA, ecstasy) is cytotoxic to BL cell lines, but its low potency, psychoactivity and neurotoxicity preclude consideration as a therapeutic drug candidate. This paper describes the discovery of novel -aryl analogues of MDMA that lack psychoactivity and reduce BL cell line viability with significantly more potency than the lead compound. Preliminary in vitro studies also indicate that the compounds are non-toxic to a relevant neuronal cell line.</div></front></TEI><affiliations><list><country><li>Australie</li><li>Canada</li><li>Royaume-Uni</li></country><region><li>Angleterre</li><li>Midlands de l'Ouest</li></region><settlement><li>Birmingham</li></settlement><orgName><li>Université de Birmingham</li></orgName></list><tree><country name="Australie"><noRegion><name sortKey="Gandy, Michael N" sort="Gandy, Michael N" uniqKey="Gandy M" first="Michael N." last="Gandy">Michael N. Gandy</name></noRegion><name sortKey="Gandy, Michael N" sort="Gandy, Michael N" uniqKey="Gandy M" first="Michael N." last="Gandy">Michael N. Gandy</name><name sortKey="Lewis, Katie" sort="Lewis, Katie" uniqKey="Lewis K" first="Katie" last="Lewis">Katie Lewis</name><name sortKey="Lewis, Katie" sort="Lewis, Katie" uniqKey="Lewis K" first="Katie" last="Lewis">Katie Lewis</name><name sortKey="Martin Iverson, Mathew T" sort="Martin Iverson, Mathew T" uniqKey="Martin Iverson M" first="Mathew T." last="Martin-Iverson">Mathew T. Martin-Iverson</name><name sortKey="Mcildowie, Matthew" sort="Mcildowie, Matthew" uniqKey="Mcildowie M" first="Matthew" last="Mcildowie">Matthew Mcildowie</name><name sortKey="Mcildowie, Matthew" sort="Mcildowie, Matthew" uniqKey="Mcildowie M" first="Matthew" last="Mcildowie">Matthew Mcildowie</name><name sortKey="Millar, Zak A" sort="Millar, Zak A" uniqKey="Millar Z" first="Zak A." last="Millar">Zak A. Millar</name><name sortKey="Nguyen, Blake" sort="Nguyen, Blake" uniqKey="Nguyen B" first="Blake" last="Nguyen">Blake Nguyen</name><name sortKey="Nguyen, Blake" sort="Nguyen, Blake" uniqKey="Nguyen B" first="Blake" last="Nguyen">Blake Nguyen</name><name sortKey="Piggott, Matthew J" sort="Piggott, Matthew J" uniqKey="Piggott M" first="Matthew J." last="Piggott">Matthew J. Piggott</name><name sortKey="Piggott, Matthew J" sort="Piggott, Matthew J" uniqKey="Piggott M" first="Matthew J." last="Piggott">Matthew J. Piggott</name><name sortKey="Tindiglia, David" sort="Tindiglia, David" uniqKey="Tindiglia D" first="David" last="Tindiglia">David Tindiglia</name><name sortKey="Wagg, Keith" sort="Wagg, Keith" uniqKey="Wagg K" first="Keith" last="Wagg">Keith Wagg</name></country><country name="Royaume-Uni"><region name="Angleterre"><name sortKey="Wasik, Agata M" sort="Wasik, Agata M" uniqKey="Wasik A" first="Agata M." last="Wasik">Agata M. Wasik</name></region><name sortKey="Barnes, Nicholas M" sort="Barnes, Nicholas M" uniqKey="Barnes N" first="Nicholas M." last="Barnes">Nicholas M. Barnes</name><name sortKey="Gordon, John" sort="Gordon, John" uniqKey="Gordon J" first="John" last="Gordon">John Gordon</name></country><country name="Canada"><noRegion><name sortKey="Salomonczyk, Danielle" sort="Salomonczyk, Danielle" uniqKey="Salomonczyk D" first="Danielle" last="Salomonczyk">Danielle Salomonczyk</name></noRegion><name sortKey="Brotchie, Jonathan M" sort="Brotchie, Jonathan M" uniqKey="Brotchie J" first="Jonathan M." last="Brotchie">Jonathan M. Brotchie</name><name sortKey="Huot, Philippe" sort="Huot, Philippe" uniqKey="Huot P" first="Philippe" last="Huot">Philippe Huot</name><name sortKey="Johnston, Tom" sort="Johnston, Tom" uniqKey="Johnston T" first="Tom" last="Johnston">Tom Johnston</name><name sortKey="Nash, Joanne" sort="Nash, Joanne" uniqKey="Nash J" first="Joanne" last="Nash">Joanne Nash</name><name sortKey="Thiele, Sherri" sort="Thiele, Sherri" uniqKey="Thiele S" first="Sherri" last="Thiele">Sherri Thiele</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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