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A novel class of piperidones exhibit potent, selective and pro-apoptotic anti-leukemia properties.
Nunes, Larissa M; Hossain, Mohammad; Varela-Ramirez, Armando; DAS, Umashankar; Ayala-Marin, Yoshira M; Dimmock, Jonathan R; Aguilera, Renato J.
Afiliación
  • Nunes LM; Cytometry, Imaging and Screening Core Facility, Border Biomedical Research Center, Department of Biological Sciences, The University of Texas at El Paso, El Paso, TX 79968-0519, USA.
  • Hossain M; Drug Discovery and Development Research Group, College of Pharmacy and Nutrition, University of Saskatchewan, Saskatoon, SK S7N 5C9, Canada.
  • Varela-Ramirez A; Cytometry, Imaging and Screening Core Facility, Border Biomedical Research Center, Department of Biological Sciences, The University of Texas at El Paso, El Paso, TX 79968-0519, USA.
  • DAS U; Drug Discovery and Development Research Group, College of Pharmacy and Nutrition, University of Saskatchewan, Saskatoon, SK S7N 5C9, Canada.
  • Ayala-Marin YM; Cytometry, Imaging and Screening Core Facility, Border Biomedical Research Center, Department of Biological Sciences, The University of Texas at El Paso, El Paso, TX 79968-0519, USA.
  • Dimmock JR; Drug Discovery and Development Research Group, College of Pharmacy and Nutrition, University of Saskatchewan, Saskatoon, SK S7N 5C9, Canada.
  • Aguilera RJ; Cytometry, Imaging and Screening Core Facility, Border Biomedical Research Center, Department of Biological Sciences, The University of Texas at El Paso, El Paso, TX 79968-0519, USA.
Oncol Lett ; 11(6): 3842-3848, 2016 Jun.
Article en En | MEDLINE | ID: mdl-27313705
In the present pre-clinical study, a series of 1-[3-(2-methoxyethylthio)-propionyl]-3,5- bis(benzylidene)-4 piperidones and structurally-related compounds were observed to be cytotoxic in vitro to three human leukemia cell lines, namely Nalm-6, CEM and Jurkat. The 50% cytotoxic concentration (CC50) values of the three cell lines ranged between 0.9-126.4 µM and 0.3-11.7 µM at 24 and 48 h subsequent to exposure, respectively. The two lead compounds with sub-micromolar CC50 concentrations, 1-(2-methoxyethylthio-propionyl)-3,5-bis(benzylidene)-4 piperidone (2a) and 3,5-bis(4-fluorobenzylidene)-1-[3-(2-methoxyethyl sulfinyl)-propionyl]-4-piperidone (3e), were selected for additional analyses. Several strategies were undertaken to determine whether the above piperidones caused cell death via apoptosis or necrosis on T-lymphocyte leukemia Jurkat cells. The results revealed that the two piperidones caused phosphatidylserine externalization, mitochondrial depolarization and activation of caspase-3, which are all biochemical hallmarks of apoptosis. In addition, the selected piperidones displayed selective cytotoxicity towards leukemia cells, and were less toxic in non-cancerous control cells. Therefore, the findings of the present study revealed that the novel piperidones 2a and 3e exert a selective cytotoxic effect on lymphocyte leukemia cells by favoring the activation of the intrinsic/mitochondrial apoptotic pathway.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Oncol Lett Año: 2016 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Grecia
Texto completo
Añadir a Mi BVS
Imprimir
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Oncol Lett Año: 2016 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Grecia