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

Journal article

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.

Authors: Simoni, D; Gebbia, N; Invidiata, F; Eleopra, M; Marchetti, P

• Publication status: Published
• Journal: Journal of medicinal chemistry
• Volume: 51
• Issue: 21
• Pages: 6800-6807
• Publication date: 2008-11-01
• DOI: 10.1021/jm801003y
• EISSN: 1520-4804
• ISSN: 0022-2623
• Language: English
• Keywords: Mice, SCID; Amines; Humans; Mice; Lymphocyte Activation; Cell Line, Tumor; Drug Design; Animals; Receptors, Antigen, T-Cell, gamma-delta; Antineoplastic Agents; Molecular Structure; Structure-Activity Relationship; Apoptosis; Diphosphonates