Design And Synthesis Of N-acylated Aza-goniothalamin Derivatives And Evaluation Of Their In Vitro And In Vivo Antitumor Activity.

dc.creatorBarcelos, Rosimeire Coura
dc.creatorPastre, Julio Cezar
dc.creatorVendramini-Costa, Débora Barbosa
dc.creatorCaixeta, Vanessa
dc.creatorLongato, Giovanna Barbarini
dc.creatorMonteiro, Paula Araújo
dc.creatorde Carvalho, João Ernesto
dc.creatorPilli, Ronaldo Aloise
dc.date2014-Dec
dc.date2015-11-27T13:43:27Z
dc.date2015-11-27T13:43:27Z
dc.date.accessioned2018-03-29T01:22:09Z
dc.date.available2018-03-29T01:22:09Z
dc.identifierChemmedchem. v. 9, n. 12, p. 2725-43, 2014-Dec.
dc.identifier1860-7187
dc.identifier10.1002/cmdc.201402292
dc.identifierhttp://www.ncbi.nlm.nih.gov/pubmed/25263285
dc.identifierhttp://repositorio.unicamp.br/jspui/handle/REPOSIP/201758
dc.identifier25263285
dc.identifier.urihttp://repositorioslatinoamericanos.uchile.cl/handle/2250/1301991
dc.descriptionHerein we describe the synthesis of a focused library of compounds based on the structure of goniothalamin (1) and the evaluation of the potential antitumor activity of the compounds. N-Acylation of aza-goniothalamin (2) restored the in vitro antiproliferative activity of this family of compounds. 1-(E)-But-2-enoyl-6-styryl-5,6-dihydropyridin-2(1H)-one (18) displayed enhanced antiproliferative activity. Both goniothalamin (1) and derivative 18 led to reactive oxygen species generation in PC-3 cells, which was probably a signal for caspase-dependent apoptosis. Treatment with derivative 18 promoted Annexin V/7-aminoactinomycin D double staining, which indicated apoptosis, and also led to G2 /M cell-cycle arrest. In vivo studies in Ehrlich ascitic and solid tumor models confirmed the antitumor activity of goniothalamin (1), without signs of toxicity. However, derivative 18 exhibited an unexpectedly lower in vivo antitumor activity, despite the treatments being administered at the same site of inoculation. Contrary to its in vitro profile, aza-goniothalamin (2) inhibited Ehrlich tumor growth, both on the ascitic and solid forms. Our findings highlight the importance of in vivo studies in the search for new candidates for cancer treatment.
dc.description9
dc.description2725-43
dc.languageeng
dc.relationChemmedchem
dc.relationChemMedChem
dc.rightsfechado
dc.rights© 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
dc.sourcePubMed
dc.subjectAcylation
dc.subjectAntitumor Agents
dc.subjectAza Compounds
dc.subjectCytotoxicity
dc.subjectGoniothalamin
dc.titleDesign And Synthesis Of N-acylated Aza-goniothalamin Derivatives And Evaluation Of Their In Vitro And In Vivo Antitumor Activity.
dc.typeArtículos de revistas


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