Please use this identifier to cite or link to this item: http://hdl.handle.net/10553/41501
DC FieldValueLanguage
dc.contributor.authorRomagnoli, Romeoen_US
dc.contributor.authorPrencipe, Filippoen_US
dc.contributor.authorLopez-Cara, Luisa Carlotaen_US
dc.contributor.authorOliva, Paolaen_US
dc.contributor.authorBaraldi, Stefaniaen_US
dc.contributor.authorBaraldi, Pier Giovannien_US
dc.contributor.authorEstévez-Sarmiento, Franciscoen_US
dc.contributor.authorQuintana, Joseen_US
dc.contributor.authorEstévez, Franciscoen_US
dc.contributor.otherEstevez, Francisco
dc.contributor.otherLOPEZ-CARA, LUISA CARLOTA
dc.date.accessioned2018-07-09T12:26:10Z-
dc.date.available2018-07-09T12:26:10Z-
dc.date.issued2018en_US
dc.identifier.issn1475-6366en_US
dc.identifier.urihttp://hdl.handle.net/10553/41501-
dc.description.abstractThe combination of two pharmacophores into a single molecule represents one of the methods that can be adopted for the synthesis of new anticancer molecules. To investigate the influence of the position of the pyridine nitrogen on biological activity, two different series of α-bromoacryloylamido indolyl pyridinyl propenones 3a–h and 4a–d were designed and synthesized by a pharmacophore hybridization approach and evaluated for their antiproliferative activity against a panel of six human cancer cell lines. These hybrid molecules were prepared to combine the α-bromoacryloyl moiety with two series of indole-inspired chalcone analogues, possessing an indole derivative and a 3- or 4-pyridine ring, respectively, linked on either side of 2-propen-1-one system. The structure-activity relationship was also investigated by the insertion of alkyl or benzyl moieties at the N-1 position of the indole nucleus. We found that most of the newly synthesized displayed high antiproliferative activity against U-937, MOLT-3, K-562, and NALM-6 leukaemia cell lines, with one-digit to double-digit nanomolar IC50values. The antiproliferative activities of 3-pyridinyl derivatives 3f–h revealed that N-benzyl indole analogues generally exhibited lower activity compared to N-H or N-alkyl derivatives 3a–b and 3c–e, respectively. Moreover, cellular mechanism studies elucidated that compound 4a induced apoptosis along with a decrease of mitochondrial membrane potential and activated caspase-3 in a concentration-dependent manner.en_US
dc.languageengen_US
dc.relation.ispartofJournal of Enzyme Inhibition and Medicinal Chemistryen_US
dc.sourceJournal of Enzyme Inhibition and Medicinal Chemistry[ISSN 1475-6366],v. 33, p. 727-742en_US
dc.subject32 Ciencias médicasen_US
dc.subject.otherApoptosisen_US
dc.subject.otherIndole-based chalconeen_US
dc.subject.otherα-bromoacryloyl moietyen_US
dc.subject.otherIn vitro antiproliferative activityen_US
dc.subject.otherCaspasesen_US
dc.titleSynthesis and biological evaluation of alpha-bromoacryloylamido indolyl pyridinyl propenones as potent apoptotic inducers in human leukaemia cellsen_US
dc.typeinfo:eu-repo/semantics/Articlees
dc.typeArticlees
dc.identifier.doi10.1080/14756366.2018.1450749
dc.identifier.scopus85045133032
dc.identifier.isi000429336700001
dcterms.isPartOfJournal Of Enzyme Inhibition And Medicinal Chemistry
dcterms.sourceJournal Of Enzyme Inhibition And Medicinal Chemistry[ISSN 1475-6366],v. 33 (1), p. 727-742
dc.contributor.authorscopusid7101729609
dc.contributor.authorscopusid56176991100
dc.contributor.authorscopusid10640397600
dc.contributor.authorscopusid57189465631
dc.contributor.authorscopusid16027688700
dc.contributor.authorscopusid7101681318
dc.contributor.authorscopusid57195986997
dc.contributor.authorscopusid8681043500
dc.contributor.authorscopusid7003810011
dc.description.lastpage742-
dc.description.firstpage727-
dc.relation.volume33-
dc.investigacionCiencias de la Saluden_US
dc.type2Artículoen_US
dc.identifier.wosWOS:000429336700001-
dc.contributor.daisngid32727
dc.contributor.daisngid2784723
dc.contributor.daisngid736149
dc.contributor.daisngid4839036
dc.contributor.daisngid1379634
dc.contributor.daisngid38403
dc.contributor.daisngid9065323
dc.contributor.daisngid128315
dc.contributor.daisngid384944
dc.identifier.investigatorRIDK-5125-2014
dc.identifier.investigatorRIDF-9686-2014
dc.contributor.wosstandardWOS:Romagnoli, R
dc.contributor.wosstandardWOS:Prencipe, F
dc.contributor.wosstandardWOS:Lopez-Cara, LC
dc.contributor.wosstandardWOS:Oliva, P
dc.contributor.wosstandardWOS:Baraldi, S
dc.contributor.wosstandardWOS:Baraldi, PG
dc.contributor.wosstandardWOS:Estevez-Sarmiento, F
dc.contributor.wosstandardWOS:Quintana, J
dc.contributor.wosstandardWOS:Estevez, F
dc.date.coverdateEnero 2018
dc.identifier.ulpgces
dc.description.sjr0,781
dc.description.jcr4,027
dc.description.sjrqQ2
dc.description.jcrqQ1
item.fulltextSin texto completo-
item.grantfulltextnone-
crisitem.author.deptBioquímica Farmacológica-
crisitem.author.deptIU de Investigaciones Biomédicas y Sanitarias-
crisitem.author.deptDepartamento de Bioquímica y Biología Molecular, Fisiología, Genética e Inmunología.-
crisitem.author.deptBioquímica Farmacológica-
crisitem.author.deptIU de Investigaciones Biomédicas y Sanitarias-
crisitem.author.deptDepartamento de Bioquímica y Biología Molecular, Fisiología, Genética e Inmunología.-
crisitem.author.deptBioquímica Farmacológica-
crisitem.author.deptIU de Investigaciones Biomédicas y Sanitarias-
crisitem.author.deptDepartamento de Bioquímica y Biología Molecular, Fisiología, Genética e Inmunología.-
crisitem.author.orcid0000-0002-9728-2774-
crisitem.author.orcid0000-0001-8225-4538-
crisitem.author.orcid0000-0002-9728-2774-
crisitem.author.parentorgIU de Investigaciones Biomédicas y Sanitarias-
crisitem.author.parentorgIU de Investigaciones Biomédicas y Sanitarias-
crisitem.author.parentorgIU de Investigaciones Biomédicas y Sanitarias-
crisitem.author.fullNameEstévez Rosas, Francisco Jesús-
crisitem.author.fullNameQuintana Aguiar, José Martín-
crisitem.author.fullNameEstévez Rosas, Francisco Jesús-
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