Design, synthesis, and biological evaluation of novel aminobisphosphonates possessing an in vivo antitumor activity through a γδ-T lymphocytes-mediated activation mechanism

Daniele Simoni, Nicola Gebbia, Francesco Paolo Invidiata, Marco Eleopra, Paolo Marchetti, Riccardo Rondanin, Riccardo Baruchello, Stefano Provera, Carla Marchioro, Manlio Tolomeo, Luciana Marinelli, Vittorio Limongelli, Ettore Novellino, Aaron Kwaasi, James Dunford, Simona Buccheri, Nadia Caccamo, Francesco Dieli

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Abstract

A small series of aminobisphosphonates (N-BPs) structurally related to zoledronic acid was synthesized with the aim of improving activity toward activation of human γδ T cells and in turn their in vivo antitumor activity. The absence of the 1-OH moiety, together with the position and the different basicity of the nitrogen, appears crucial for antitumor activity. In comparison to zoledronic acid, compound 6a shows a greater ability to activate γδ T cells expression (100 times more) and a proapoptotic effect that is better than zoledronic acid. The potent activation of γδ T cells, in addition to evidence of the in vivo antitumor activity of 6a, suggests it may be a new potential drug candidate for cancer treatment.

Original languageEnglish
Pages (from-to)6800-6807
Number of pages8
JournalJournal of Medicinal Chemistry
Volume51
Issue number21
DOIs
Publication statusPublished - Nov 13 2008

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ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery

Cite this

Simoni, D., Gebbia, N., Invidiata, F. P., Eleopra, M., Marchetti, P., Rondanin, R., Baruchello, R., Provera, S., Marchioro, C., Tolomeo, M., Marinelli, L., Limongelli, V., Novellino, E., Kwaasi, A., Dunford, J., Buccheri, S., Caccamo, N., & Dieli, F. (2008). Design, synthesis, and biological evaluation of novel aminobisphosphonates possessing an in vivo antitumor activity through a γδ-T lymphocytes-mediated activation mechanism. Journal of Medicinal Chemistry, 51(21), 6800-6807. https://doi.org/10.1021/jm801003y