Discovery of cytotoxic and pro-apoptotic compounds against leukemia cells: Tert-butyl-4-[(3-nitrophenoxy) methyl]-2,2-dimethyloxazolidine-3-carboxylate
| Autor(a) principal: | |
|---|---|
| Data de Publicação: | 2011 |
| Outros Autores: | , , , , , , , , |
| Tipo de documento: | Artigo |
| Idioma: | eng |
| Título da fonte: | Repositório Institucional da FIOCRUZ (ARCA) |
| Texto Completo: | https://www.arca.fiocruz.br/handle/icict/9000 |
Resumo: | Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Belo Horizonte, MG, Brasil |
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Pinto, Mauro Cunha XavierDias, Danielle FerreiraDel Puerto, Helen LimaMartins, Almir de SousaCarvalho, Andréa TeixeiraMartins Filho, Olindo AssisBadet, BernardDurand, PhilippeAlves, Ricardo JoséFagundes, Elaine Maria de Souza2014-11-28T13:36:12Z2014-11-28T13:36:12Z2011PINTO, 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, 2011.0024-320510.1016/j.lfs.2011.09.012https://www.arca.fiocruz.br/handle/icict/9000engElsevierDiscovery of cytotoxic and pro-apoptotic compounds against leukemia cells: Tert-butyl-4-[(3-nitrophenoxy) methyl]-2,2-dimethyloxazolidine-3-carboxylateinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleUniversidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Belo Horizonte, MG, BrasilUniversidade Federal de Minas Gerais. Faculdade de Farmácia. Belo Horizonte, MG, BrasilUniversidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Belo Horizonte, MG, BrasilUniversidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Belo Horizonte, MG, BrasilFundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Belo Horizonte, MG, BrasilFundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Belo Horizonte, MG, BrasilInstitut de Chimie des Substances Naturelles-CNRS. Gif-sur-Yvette, FranceInstitut de Chimie des Substances Naturelles-CNRS. Gif-sur-Yvette, FranceUniversidade Federal de Minas Gerais. Faculdade de Farmácia. Belo Horizonte, MG, BrasilUniversidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Belo Horizonte, MG, BrasilAims: 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.ApoptosisDrug discoveryHit compoundScaffoldAnti-cancerinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da FIOCRUZ (ARCA)instname:Fundação Oswaldo Cruz (FIOCRUZ)instacron:FIOCRUZLICENSElicense.txtlicense.txttext/plain; charset=utf-81914https://www.arca.fiocruz.br/bitstream/icict/9000/1/license.txt7d48279ffeed55da8dfe2f8e81f3b81fMD51ORIGINALDiscovery of cytotoxic and pro-apoptotic compounds against leukemia cells.pdfDiscovery of cytotoxic and pro-apoptotic compounds against leukemia cells.pdfapplication/pdf952430https://www.arca.fiocruz.br/bitstream/icict/9000/2/Discovery%20of%20cytotoxic%20and%20pro-apoptotic%20compounds%20against%20leukemia%20cells.pdfc80a532f9fefe7ae8cc25e5c90d280adMD52TEXTDiscovery of cytotoxic and pro-apoptotic compounds against leukemia cells.pdf.txtDiscovery of cytotoxic and pro-apoptotic compounds against leukemia cells.pdf.txtExtracted texttext/plain48892https://www.arca.fiocruz.br/bitstream/icict/9000/3/Discovery%20of%20cytotoxic%20and%20pro-apoptotic%20compounds%20against%20leukemia%20cells.pdf.txte6d25b855b9ffe6a81e676a37a5c1f0cMD53icict/90002019-06-19 10:12:49.71oai:www.arca.fiocruz.br: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ório InstitucionalPUBhttps://www.arca.fiocruz.br/oai/requestrepositorio.arca@fiocruz.bropendoar:21352019-06-19T13:12:49Repositório Institucional da FIOCRUZ (ARCA) - Fundação Oswaldo Cruz (FIOCRUZ)false |
| dc.title.pt_BR.fl_str_mv |
Discovery of cytotoxic and pro-apoptotic compounds against leukemia cells: Tert-butyl-4-[(3-nitrophenoxy) methyl]-2,2-dimethyloxazolidine-3-carboxylate |
| title |
Discovery of cytotoxic and pro-apoptotic compounds against leukemia cells: Tert-butyl-4-[(3-nitrophenoxy) methyl]-2,2-dimethyloxazolidine-3-carboxylate |
| spellingShingle |
Discovery of cytotoxic and pro-apoptotic compounds against leukemia cells: Tert-butyl-4-[(3-nitrophenoxy) methyl]-2,2-dimethyloxazolidine-3-carboxylate Pinto, Mauro Cunha Xavier Apoptosis Drug discovery Hit compound Scaffold Anti-cancer |
| title_short |
Discovery of cytotoxic and pro-apoptotic compounds against leukemia cells: Tert-butyl-4-[(3-nitrophenoxy) methyl]-2,2-dimethyloxazolidine-3-carboxylate |
| title_full |
Discovery of cytotoxic and pro-apoptotic compounds against leukemia cells: Tert-butyl-4-[(3-nitrophenoxy) methyl]-2,2-dimethyloxazolidine-3-carboxylate |
| title_fullStr |
Discovery of cytotoxic and pro-apoptotic compounds against leukemia cells: Tert-butyl-4-[(3-nitrophenoxy) methyl]-2,2-dimethyloxazolidine-3-carboxylate |
| title_full_unstemmed |
Discovery of cytotoxic and pro-apoptotic compounds against leukemia cells: Tert-butyl-4-[(3-nitrophenoxy) methyl]-2,2-dimethyloxazolidine-3-carboxylate |
| title_sort |
Discovery of cytotoxic and pro-apoptotic compounds against leukemia cells: Tert-butyl-4-[(3-nitrophenoxy) methyl]-2,2-dimethyloxazolidine-3-carboxylate |
| author |
Pinto, Mauro Cunha Xavier |
| author_facet |
Pinto, Mauro Cunha Xavier Dias, Danielle Ferreira Del Puerto, Helen Lima Martins, Almir de Sousa Carvalho, Andréa Teixeira Martins Filho, Olindo Assis Badet, Bernard Durand, Philippe Alves, Ricardo José Fagundes, Elaine Maria de Souza |
| author_role |
author |
| author2 |
Dias, Danielle Ferreira Del Puerto, Helen Lima Martins, Almir de Sousa Carvalho, Andréa Teixeira Martins Filho, Olindo Assis Badet, Bernard Durand, Philippe Alves, Ricardo José Fagundes, Elaine Maria de Souza |
| author2_role |
author author author author author author author author author |
| dc.contributor.author.fl_str_mv |
Pinto, Mauro Cunha Xavier Dias, Danielle Ferreira Del Puerto, Helen Lima Martins, Almir de Sousa Carvalho, Andréa Teixeira Martins Filho, Olindo Assis Badet, Bernard Durand, Philippe Alves, Ricardo José Fagundes, Elaine Maria de Souza |
| dc.subject.en.pt_BR.fl_str_mv |
Apoptosis Drug discovery Hit compound Scaffold Anti-cancer |
| topic |
Apoptosis Drug discovery Hit compound Scaffold Anti-cancer |
| description |
Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Belo Horizonte, MG, Brasil |
| publishDate |
2011 |
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2011 |
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2014-11-28T13:36:12Z |
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2014-11-28T13:36:12Z |
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info:eu-repo/semantics/publishedVersion |
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info:eu-repo/semantics/article |
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PINTO, 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. |
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https://www.arca.fiocruz.br/handle/icict/9000 |
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0024-3205 10.1016/j.lfs.2011.09.012 |
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PINTO, 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. 0024-3205 10.1016/j.lfs.2011.09.012 |
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Elsevier |
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