Please use this identifier to cite or link to this item: http://hdl.handle.net/10553/50574
DC FieldValueLanguage
dc.contributor.authorBaraldi, Pier Giovannien_US
dc.contributor.authorDel Carmen Nunez, Mariaen_US
dc.contributor.authorTabrizi, Mojgan Aghazadehen_US
dc.contributor.authorDe Clercq, Eriken_US
dc.contributor.authorBalzarini, Janen_US
dc.contributor.authorBermejo, Jaimeen_US
dc.contributor.authorEstévez, Franciscoen_US
dc.contributor.authorRomagnoli, Romeoen_US
dc.contributor.otherBaraldi, Pier Giovanni-
dc.contributor.otherNunez-Carretero, M del Carmen-
dc.contributor.otherAghazadeh Tabrizi, Mojgan-
dc.contributor.otherRomagnoli, Romeo-
dc.contributor.otherEstevez, Francisco-
dc.contributor.otherDe Clercq, Erik-
dc.date.accessioned2018-11-24T17:06:39Z-
dc.date.available2018-11-24T17:06:39Z-
dc.date.issued2004en_US
dc.identifier.issn0022-2623en_US
dc.identifier.urihttp://hdl.handle.net/10553/50574-
dc.description.abstractWe have synthesized and evaluated a series of hybrids of polypyrrole minor groove binders structurally related to the natural antitumor agent distamycin A, and α-methylene-γ-butyrolactones with methyl, phenyl, and 4-substituted phenyl groups at the lactone C(γ) position, denoted 5-17, for in vitro cytotoxic activity against a variety of cancer cell lines. The apoptotic and cytotoxic activities against several tumor cell lines are reported and discussed in terms of their structural differences in relation to both the number of N-methylpyrrole rings and the type of the alkylating unit tethered to the oligopeptidic frame. It may be noted that in general, and especially for 11, 12, and 17, the cytotoxicity of the hybrids was much greater than that of the α-methylene-γ-butyrolactone units 24a-g alone. Using the human leukemia cell line HL-60, we have tested the effects of a selected series of compounds on programmed cell death (apoptosis). The results clearly indicate that 11, 12, and 17, but not 9, are able to induce apoptosis as demonstrated from (i) identification of nuclear changes associated with apoptosis using fluorescence microscopy and (ii) by DNA laddering on agarose gel electrophoresis. Compound 12 was the most potent, especially after a short incubation period. It induced extensive hydrolysis of poly ADP-ribose polymerase (PARP), considered to be a hallmark of apoptosis, which plays a critical role in chromatin architecture and DNA metabolism.en_US
dc.languageengen_US
dc.relation.ispartofJournal of Medicinal Chemistryen_US
dc.sourceJournal Of Medicinal Chemistry[ISSN 0022-2623],v. 47 (11), p. 2877-2886en_US
dc.subject3201 Ciencias clínicasen_US
dc.subject320104 Patología clínicaen_US
dc.subject.otherLactone Tumor Inhibitorsen_US
dc.subject.otherAntitumor Agentsen_US
dc.subject.otherDistamycinen_US
dc.subject.otherSpecificityen_US
dc.subject.otherNetropsinen_US
dc.titleDesign, synthesis, and biological evaluation of hybrid molecules containing alpha-methylene-gamma-butyrolactones and polypyrrole minor groove bindersen_US
dc.typeinfo:eu-repo/semantics/Articleen_US
dc.typeArticleen_US
dc.identifier.doi10.1021/jm031104yen_US
dc.identifier.scopus2442645224-
dc.identifier.isi000221456700019-
dcterms.isPartOfJournal Of Medicinal Chemistry-
dcterms.sourceJournal Of Medicinal Chemistry[ISSN 0022-2623],v. 47 (11), p. 2877-2886-
dc.contributor.authorscopusid7101681318-
dc.contributor.authorscopusid6508020494-
dc.contributor.authorscopusid35458610100-
dc.contributor.authorscopusid35399610800-
dc.contributor.authorscopusid36049696300-
dc.contributor.authorscopusid7101636723-
dc.contributor.authorscopusid7003810011-
dc.contributor.authorscopusid7101729609-
dc.description.lastpage2886en_US
dc.identifier.issue11-
dc.description.firstpage2877en_US
dc.relation.volume47en_US
dc.investigacionCiencias de la Saluden_US
dc.type2Artículoen_US
dc.identifier.wosWOS:000221456700019-
dc.contributor.daisngid38403-
dc.contributor.daisngid1118925-
dc.contributor.daisngid1702461-
dc.contributor.daisngid240947-
dc.contributor.daisngid132-
dc.contributor.daisngid233-
dc.contributor.daisngid5695465-
dc.contributor.daisngid384944-
dc.contributor.daisngid32727-
dc.identifier.investigatorRIDB-7933-2017-
dc.identifier.investigatorRIDL-7150-2014-
dc.identifier.investigatorRIDI-9169-2014-
dc.identifier.investigatorRIDG-9887-2015-
dc.identifier.investigatorRIDK-5125-2014-
dc.identifier.investigatorRIDNo ID-
dc.description.numberofpages10en_US
dc.utils.revisionen_US
dc.contributor.wosstandardWOS:Baraldi, PG-
dc.contributor.wosstandardWOS:Nunez, MD-
dc.contributor.wosstandardWOS:Tabrizi, MA-
dc.contributor.wosstandardWOS:De Clercq, E-
dc.contributor.wosstandardWOS:Balzarini, J-
dc.contributor.wosstandardWOS:Bermejo, J-
dc.contributor.wosstandardWOS:Estevez, F-
dc.contributor.wosstandardWOS:Romagnoli, R-
dc.date.coverdateMayo 2004en_US
dc.identifier.ulpgcen_US
dc.contributor.buulpgcBU-MEDen_US
dc.description.jcr5,076-
dc.description.jcrqQ1-
dc.description.scieSCIE-
item.grantfulltextnone-
item.fulltextSin texto completo-
crisitem.author.deptGIR Bioquímica 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.parentorgIU de Investigaciones Biomédicas y Sanitarias-
crisitem.author.fullNameEstévez Rosas, Francisco Jesús-
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