A novel class of piperidones exhibit potent, selective and pro‑apoptotic anti‑leukemia properties

  • Authors:
    • Larissa M Nunes
    • Mohammad Hossain
    • Armando Varela‑Ramirez
    • Umashankar Das
    • Yoshira M Ayala‑Marin
    • Jonathan R Dimmock
    • Renato J Aguilera
  • View Affiliations

  • Published online on: April 20, 2016     https://doi.org/10.3892/ol.2016.4480
  • Pages: 3842-3848
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Abstract

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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June-2016
Volume 11 Issue 6

Print ISSN: 1792-1074
Online ISSN:1792-1082

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Spandidos Publications style
Nunes LM, Hossain M, Varela‑Ramirez A, Das U, Ayala‑Marin YM, Dimmock JR and Aguilera RJ: A novel class of piperidones exhibit potent, selective and pro‑apoptotic anti‑leukemia properties. Oncol Lett 11: 3842-3848, 2016
APA
Nunes, L.M., Hossain, M., Varela‑Ramirez, A., Das, U., Ayala‑Marin, Y.M., Dimmock, J.R., & Aguilera, R.J. (2016). A novel class of piperidones exhibit potent, selective and pro‑apoptotic anti‑leukemia properties. Oncology Letters, 11, 3842-3848. https://doi.org/10.3892/ol.2016.4480
MLA
Nunes, L. M., Hossain, M., Varela‑Ramirez, A., Das, U., Ayala‑Marin, Y. M., Dimmock, J. R., Aguilera, R. J."A novel class of piperidones exhibit potent, selective and pro‑apoptotic anti‑leukemia properties". Oncology Letters 11.6 (2016): 3842-3848.
Chicago
Nunes, L. M., Hossain, M., Varela‑Ramirez, A., Das, U., Ayala‑Marin, Y. M., Dimmock, J. R., Aguilera, R. J."A novel class of piperidones exhibit potent, selective and pro‑apoptotic anti‑leukemia properties". Oncology Letters 11, no. 6 (2016): 3842-3848. https://doi.org/10.3892/ol.2016.4480