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

J Med Chem. 2008 Nov 13;51(21):6800-7. doi: 10.1021/jm801003y. Epub 2008 Oct 21.


A small series of aminobisphosphonates (N-BPs) structurally related to zoledronic acid was synthesized with the aim of improving activity toward activation of human gammadelta 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 gammadelta T cells expression (100 times more) and a proapoptotic effect that is better than zoledronic acid. The potent activation of gammadelta 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amines / chemistry*
  • Animals
  • Antineoplastic Agents / chemical synthesis*
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects
  • Cell Line, Tumor
  • Diphosphonates / chemical synthesis*
  • Diphosphonates / chemistry
  • Diphosphonates / pharmacology*
  • Drug Design
  • Humans
  • Lymphocyte Activation / drug effects*
  • Lymphocyte Activation / immunology
  • Mice
  • Mice, SCID
  • Molecular Structure
  • Receptors, Antigen, T-Cell, gamma-delta / immunology*
  • Structure-Activity Relationship


  • Amines
  • Antineoplastic Agents
  • Diphosphonates
  • Receptors, Antigen, T-Cell, gamma-delta