Please use this identifier to cite or link to this item: https://www.arca.fiocruz.br/handle/icict/9000
Title: Discovery of cytotoxic and pro-apoptotic compounds against leukemia cells: Tert-butyl-4-[(3-nitrophenoxy) methyl]-2,2-dimethyloxazolidine-3-carboxylate
Authors: 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
Affilliation: Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Belo Horizonte, MG, Brasil
Universidade Federal de Minas Gerais. Faculdade de Farmácia. Belo Horizonte, MG, Brasil
Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Belo Horizonte, MG, Brasil
Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Belo Horizonte, MG, Brasil
Fundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Belo Horizonte, MG, Brasil
Fundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Belo Horizonte, MG, Brasil
Institut de Chimie des Substances Naturelles-CNRS. Gif-sur-Yvette, France
Institut de Chimie des Substances Naturelles-CNRS. Gif-sur-Yvette, France
Universidade Federal de Minas Gerais. Faculdade de Farmácia. Belo Horizonte, MG, Brasil
Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Belo Horizonte, MG, Brasil
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.
Keywords: Apoptosis
Drug discovery
Hit compound
Scaffold
Anti-cancer
Issue Date: 2011
Publisher: Elsevier
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.
ISSN: 0024-3205
10.1016/j.lfs.2011.09.012
Copyright: open access
Appears in Collections:MG - IRR - Artigos de Periódicos

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