Author | Pinto, Mauro Cunha Xavier | |
Author | Dias, Danielle Ferreira | |
Author | Del Puerto, Helen Lima | |
Author | Martins, Almir de Sousa | |
Author | Carvalho, Andréa Teixeira | |
Author | Martins Filho, Olindo Assis | |
Author | Badet, Bernard | |
Author | Durand, Philippe | |
Author | Alves, Ricardo José | |
Author | Fagundes, Elaine Maria de Souza | |
Access date | 2014-11-28T13:36:12Z | |
Available date | 2014-11-28T13:36:12Z | |
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 SCI, v. 89, n. 21-22, p. 786-794, 2011. | pt_BR |
ISSN | 0024-3205 | |
ISSN | 10.1016/j.lfs.2011.09.012 | |
URI | https://www.arca.fiocruz.br/handle/icict/9000 | |
Language | eng | pt_BR |
Publisher | Elsevier | pt_BR |
Rights | open access | pt_BR |
Title | Discovery of cytotoxic and pro-apoptotic compounds against leukemia cells: Tert-butyl-4-[(3-nitrophenoxy) methyl]-2,2-dimethyloxazolidine-3-carboxylate | pt_BR |
Type | Article | pt_BR |
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 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. | pt_BR |
Affilliation | Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Belo Horizonte, MG, Brasil | pt_BR |
Affilliation | Universidade Federal de Minas Gerais. Faculdade de Farmácia. Belo Horizonte, MG, Brasil | pt_BR |
Affilliation | Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Belo Horizonte, MG, Brasil | pt_BR |
Affilliation | Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Belo Horizonte, MG, Brasil | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Belo Horizonte, MG, Brasil | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Belo Horizonte, MG, Brasil | pt_BR |
Affilliation | Institut de Chimie des Substances Naturelles-CNRS. Gif-sur-Yvette, France | pt_BR |
Affilliation | Institut de Chimie des Substances Naturelles-CNRS. Gif-sur-Yvette, France | pt_BR |
Affilliation | Universidade Federal de Minas Gerais. Faculdade de Farmácia. Belo Horizonte, MG, Brasil | pt_BR |
Affilliation | Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Belo Horizonte, MG, Brasil | pt_BR |
Subject | Apoptosis | pt_BR |
Subject | Drug discovery | pt_BR |
Subject | Hit compound | pt_BR |
Subject | Scaffold | pt_BR |
Subject | Anti-cancer | pt_BR |