Novel phthalimide derivatives with TNF-α and IL-1β expression inhibitory and apoptotic inducing properties

L.C.D. Coêlho, M.V. De Oliveira Cardoso, D.R.M.M. Moreira, P.A.T. De Moraes Gomes, S.M.T. Cavalcanti, A.R. Oliveira, G.B. De Oliveira Filho, L.R. Pessoa De Siqueira, M. De Oliveira Barbosa, E.F. De Oliveira Borba, T.G. Da Silva, Belinda Kaskow, Mahdad Karimi, Lawrence Abraham, A.C.L. Leite

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Abstract

Modulation of the immune system is an emerging concept in the control of tumor growth. Bearing in mind the pharmacological properties of thalidomide and its phthalimide derivatives, we describe here the structural design, synthesis and pharmacological evaluation of N-acylhydrazones derived from phthalimide. The ability of these N-acylhydrazones in inhibiting the secretion of TNF-α in stimulated cells as well as in inhibiting the transcription of the TNF-α gene was evaluated. We identified N-acylhydrazones 6b and 9c, which substantially impaired TNF-α secretion, expression and reduced IL-1β production similar to thalidomide or Revlimid. N-Acylhydrazone 9c was also able to induce apoptosis in Jurkat cells, however it does not have either antiproliferative properties or cytotoxicity for mouse splenocytes. Beyond that, we have assayed the ability of these compounds to induce cell death and a number of them are able to induce apoptosis. © 2014 the Partner Organisations.
Original languageEnglish
Pages (from-to)758-765
JournalMedChemComm
Volume5
Issue number6
DOIs
Publication statusPublished - 2014

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Coêlho, L. C. D., De Oliveira Cardoso, M. V., Moreira, D. R. M. M., De Moraes Gomes, P. A. T., Cavalcanti, S. M. T., Oliveira, A. R., ... Leite, A. C. L. (2014). Novel phthalimide derivatives with TNF-α and IL-1β expression inhibitory and apoptotic inducing properties. MedChemComm, 5(6), 758-765. https://doi.org/10.1039/c4md00070f