Discovery of cytotoxic and pro-apoptotic compounds against leukemia cells: Tert-butyl-4-[(3-nitrophenoxy) methyl]-2,2-dimethyloxazolidine-3-carboxylate. - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue Life Sciences Année : 2011

Discovery of cytotoxic and pro-apoptotic compounds against leukemia cells: Tert-butyl-4-[(3-nitrophenoxy) methyl]-2,2-dimethyloxazolidine-3-carboxylate.

Mauro C X Pinto
  • Fonction : Auteur
Danielle F Dias
  • Fonction : Auteur
Helen L del Puerto
  • Fonction : Auteur
Almir S Martins
  • Fonction : Auteur
Andréa Teixeira-Carvalho
  • Fonction : Auteur
Olindo A Martins-Filho
  • Fonction : Auteur
Ricardo J Alves
  • Fonction : Auteur
Elaine M Souza-Fagundes
  • Fonction : Auteur

Résumé

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.

Domaines

Chimie organique

Dates et versions

hal-00649290 , version 1 (07-12-2011)

Identifiants

Citer

Mauro C X Pinto, Danielle F Dias, Helen L del Puerto, Almir S Martins, Andréa Teixeira-Carvalho, 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, 2011, 89 (21-22), pp.786-794. ⟨10.1016/j.lfs.2011.09.012⟩. ⟨hal-00649290⟩
12 Consultations
0 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More