| Author | Pinto, Mauro Cunha Xavier | |
| Author | Dias, Danielle F. | |
| Author | Puerto, Helen L. Del | |
| Author | Martins, Almir S. | |
| Author | Carvalho, Andréa Teixeira | |
| Author | Martins Filho, Olindo Assis | |
| Author | Badet, Bernard | |
| Author | Durand, Philippe | |
| Author | Alves, Ricardo J. | |
| Author | Fagundes, Elaine Maria Souza | |
| Access date | 2023-07-21T13:49:45Z | |
| Available date | 2023-07-21T13:49:45Z | |
| Document date | 2011 | |
| Citation | 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 Sciences, v. 89, n. 21–22, 21, p. 786-794, 2011. DOI: 10.1016/j.lfs.2011.09.012 | en_US |
| ISSN | 1879-0631 | en_US |
| URI | https://www.arca.fiocruz.br/handle/icict/59708 | |
| Language | eng | en_US |
| Publisher | Elsevier Inc. | en_US |
| Rights | restricted access | |
| Title | Discovery of cytotoxic and pro-apoptotic compounds against leukemia cells: Tert-butyl-4-[(3-nitrophenoxy) methyl]-2,2-dimethyloxazolidine-3-carboxylate | en_US |
| Type | Article | |
| DOI | 10.1016/j.lfs.2011.09.012 | |
| Abstract | Aims: 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 IC(50) values. 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. (C) 2011 Elsevier Inc. All rights reserved | en_US |
| Affilliation | Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Belo Horizonte, MG, Brasil | en_US |
| Affilliation | Universidade Federal de Minas Gerais. Faculdade de Farmácia. Belo Horizonte, MG, Brasil | en_US |
| Affilliation | Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Belo Horizonte, MG, Brasil | en_US |
| Affilliation | Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Belo Horizonte, MG, Brasil | en_US |
| Affilliation | Fundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Belo Horizonte, MG, Brasil | en_US |
| Affilliation | Fundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Belo Horizonte, MG, Brasil | en_US |
| Affilliation | Institut de Chimie des Substances Naturelles-CNRS. Gif-sur-Yvette, France | en_US |
| Affilliation | Institut de Chimie des Substances Naturelles-CNRS. Gif-sur-Yvette, France | en_US |
| Affilliation | Universidade Federal de Minas Gerais. Faculdade de Farmácia. Belo Horizonte, MG, Brasil | en_US |
| Affilliation | Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Belo Horizonte, MG, Brasil | en_US |
| Subject | Apoptosis | en_US |
| Subject | Drug discovery | en_US |
| Subject | Hit compound | en_US |
| Subject | Scaffold | en_US |
| Subject | Anti-cancer | en_US |
| Embargo date | 2030-12-31 | |
