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dc.contributor.authorSweeney, Martin
dc.contributor.authorCoyle, Robert
dc.contributor.authorKavanagh, Paul
dc.contributor.authorBerezin, Andrey A.
dc.contributor.authorLo Re, Daniele
dc.contributor.authorZissimou, Georgia A.
dc.contributor.authorKoutentis, Panayiotis A.
dc.contributor.authorCarty, Michael P.
dc.contributor.authorAldabbagh, Fawaz
dc.date.accessioned2017-06-27T11:23:51Z
dc.date.issued2016-05-30
dc.identifier.citationMartin Sweeney, Robert Coyle, Paul Kavanagh, Andrey A. Berezin, Daniele Lo Re, Georgia A. Zissimou, Panayiotis A. Koutentis, Michael P. Carty, Fawaz Aldabbagh (2016) 'Discovery of anti-cancer activity for benzo[1,2,4]triazin-7-ones: Very strong correlation to pleurotin and thioredoxin reductase inhibition'. Bioorganic And Medicinal Chemistry, 24 :3565-3570. doi: http://dx.doi.org/10.1016/j.bmc.2016.05.066en_IE
dc.identifier.issn1464-3391
dc.identifier.urihttp://hdl.handle.net/10379/6599
dc.description.abstractThe thioredoxin (Trx)-thioredoxin reductase (TrxR) system plays a key role in maintaining the cellular redox balance with Trx being over-expressed in a number of cancers. Inhibition of TrxR is an important strategy for anti-cancer drug discovery. The natural product pleurotin is a well-known irreversible inhibitor of TrxR. The cytotoxicity data for benzo[1,2,4]triazin-7-ones showed very strong correlation (Pearson correlation coefficients ~0.8) to pleurotin using National Cancer Institute COMPARE analysis. A new 3-CF3 substituted benzo[1,2,4]triazin-7-one gave submicromolar inhibition of TrxR, although the parent compound 1,3-diphenylbenzo[1,2,4]triazin-7-one was more cytotoxic against cancer cell lines. Benzo[1,2,4]triazin-7-ones exhibited different types of reversible inhibition of TrxR, and cyclic voltammetry showed characteristic quasi-reversible redox processes. Cell viability studies indicated strong dependence of cytotoxicity on substitution at the 6-position of the 1,3-diphenylbenzo[1,2,4]triazin-7-one ring.en_IE
dc.description.sponsorshipF.A. thanks the Irish Research Council (IRC) for a Government of Ireland Postgraduate Scholarship for Martin Sweeney and College of Science, National University of Ireland Galway (NUI Galway) for a postgraduate scholarship for Robert Coyle. We thank the National Cancer Institute (USA), Development Therapeutic Program for providing us with a small quantity of pleurotin. P.A.K. thanks the Cyprus Research Promotion Foundation [Grants: NEAYPODOMH/NEKYP/0308/02 and YGEIA/BIOS/0308(BIE)/13], the University of Cyprus (Medium Sized Grant), and the following organizations in Cyprus for generous donations of chemicals and glassware: the State General Laboratory, the Agricultural Research Institute, the Ministry of Agriculture, Medochemie Ltd and Biotronics Ltd. Furthermore, P.A.K. thanks the A. G. Leventis Foundation for helping to establish the NMR facility in the University of Cyprus.en_IE
dc.formatapplication/pdfen_IE
dc.language.isoenen_IE
dc.publisherElsevieren_IE
dc.relation.ispartofBioorganic And Medicinal Chemistryen
dc.rightsAttribution-NonCommercial-NoDerivs 3.0 Ireland
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/3.0/ie/
dc.subjectAnti-tumoren_IE
dc.subjectBioreductionen_IE
dc.subjectHeterocyclic compounden_IE
dc.subjectNCI-DTP COMPARE programen_IE
dc.titleDiscovery of anti-cancer activity for benzo[1,2,4]triazin-7-ones: Very strong correlation to pleurotin and thioredoxin reductase inhibitionen_IE
dc.typeArticleen_IE
dc.date.updated2017-06-16T13:47:31Z
dc.identifier.doi10.1016/j.bmc.2016.05.066
dc.local.publishedsourcehttps://doi.org/10.1016/j.bmc.2016.05.066en_IE
dc.description.peer-reviewedpeer-reviewed
dc.contributor.funder|~|6201984|~|
dc.description.embargo2018-05-30
dc.internal.rssid11221635
dc.local.contactFawaz Aldabbagh, Dept. Of Chemistry, Room 111, Arts/Science Building, Nui Galway. 3120 Email: fawaz.aldabbagh@nuigalway.ie
dc.local.copyrightcheckedNo
dc.local.versionACCEPTED
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