Please use this identifier to cite or link to this item: https://www.arca.fiocruz.br/handle/icict/9000
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dc.contributor.authorPinto, Mauro Cunha Xavier
dc.contributor.authorDias, Danielle Ferreira
dc.contributor.authorDel Puerto, Helen Lima
dc.contributor.authorMartins, Almir de Sousa
dc.contributor.authorCarvalho, Andréa Teixeira
dc.contributor.authorMartins Filho, Olindo Assis
dc.contributor.authorBadet, Bernard
dc.contributor.authorDurand, Philippe
dc.contributor.authorAlves, Ricardo José
dc.contributor.authorFagundes, Elaine Maria de Souza
dc.date.accessioned2014-11-28T13:36:12Z
dc.date.available2014-11-28T13:36:12Z
dc.date.issued2011
dc.identifier.citationPINTO, Mauro Cunha Xavier et al. Discovery of cytotoxic and pro-apoptotic compounds against leukemia cells: Tert-butyl-4-[(3-nitrophenoxy) methyl]-2,2-dimethyloxazolidine-3-carboxylate. LIFE SCI, v. 89, n. 21-22, p. 786-794, 2011.
dc.identifier.issn0024-3205
dc.identifier.issn10.1016/j.lfs.2011.09.012
dc.identifier.urihttps://www.arca.fiocruz.br/handle/icict/9000
dc.language.isoeng
dc.publisherElsevier
dc.rightsopen access
dc.titleDiscovery of cytotoxic and pro-apoptotic compounds against leukemia cells: Tert-butyl-4-[(3-nitrophenoxy) methyl]-2,2-dimethyloxazolidine-3-carboxylate
dc.typeArticle
dc.description.abstractenAims: We evaluated biological activity in leukemia cells lines of R and S enantiomers of tert-butyl 4-[(3-nitrophenoxy)-methyl]-2,2-dimethyloxazolidine-3-carboxylate (BNDC). Main methods: Cytotoxic activity was assessed by MTT assay. Flow cytometry assays were used to determined DNA fragmentation (Propidium Iodide-PI staining) and phosphatidylserine exposure (Annexin-V and PI staining). DNA condensation was evaluated by fluorescence microscopy using double-staining in leukemia cells (Hoechst and PI). Caspase activities were measured using Z-VAD-FMK, a non-selective caspase inhibitor, by flow cytometry and Z-DEVD-AMC, a selective caspase-3 substrate, by fluorescence spectrometry. Key findings: Both enantiomers displayed cytotoxic activity against leukemia cell lines (HL60, HL60.Bcl-2, HL60.Bcl-XL and Jurkat) with low toxicity against human peripheral blood mononuclear cell — PBMC based on IC50values. In HL60 cell lines, compounds induce exposure of phosphatidylserine and DNA fragmentation, which could be blocked by pretreatment of cells with Z-VAD-FMK. Confirming this observation, both enantiomers induced caspase-3 activation. Additional analysis revealed an increased percentage of apoptotic cells (defined as those with fragmented nuclei and condensed chromatin) after treatment with compounds. Significance: Taken together, the results indicate that BNDC compounds exhibited cytotoxic and pro-apoptotic activities and have a potential for developing a new class of anticancer drugs.
dc.creator.affilliationUniversidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Belo Horizonte, MG, Brasil
dc.creator.affilliationUniversidade Federal de Minas Gerais. Faculdade de Farmácia. Belo Horizonte, MG, Brasil
dc.creator.affilliationUniversidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Belo Horizonte, MG, Brasil
dc.creator.affilliationUniversidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Belo Horizonte, MG, Brasil
dc.creator.affilliationFundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Belo Horizonte, MG, Brasil
dc.creator.affilliationFundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Belo Horizonte, MG, Brasil
dc.creator.affilliationInstitut de Chimie des Substances Naturelles-CNRS. Gif-sur-Yvette, France
dc.creator.affilliationInstitut de Chimie des Substances Naturelles-CNRS. Gif-sur-Yvette, France
dc.creator.affilliationUniversidade Federal de Minas Gerais. Faculdade de Farmácia. Belo Horizonte, MG, Brasil
dc.creator.affilliationUniversidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Belo Horizonte, MG, Brasil
dc.subject.enApoptosis
dc.subject.enDrug discovery
dc.subject.enHit compound
dc.subject.enScaffold
dc.subject.enAnti-cancer
Appears in Collections:MG - IRR - Artigos de Periódicos

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