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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.

Original publication




Journal article


J med chem

Publication Date





6800 - 6807


Amines, Animals, Antineoplastic Agents, Apoptosis, Cell Line, Tumor, Diphosphonates, Drug Design, Humans, Lymphocyte Activation, Mice, Mice, SCID, Molecular Structure, Receptors, Antigen, T-Cell, gamma-delta, Structure-Activity Relationship