TY - JOUR
T1 - Design, synthesis, and biological evaluation of novel aminobisphosphonates possessing an in vivo antitumor activity through a γδ-T lymphocytes-mediated activation mechanism
AU - Simoni, Daniele
AU - Gebbia, Nicola
AU - Invidiata, Francesco Paolo
AU - Eleopra, Marco
AU - Marchetti, Paolo
AU - Rondanin, Riccardo
AU - Baruchello, Riccardo
AU - Provera, Stefano
AU - Marchioro, Carla
AU - Tolomeo, Manlio
AU - Marinelli, Luciana
AU - Limongelli, Vittorio
AU - Novellino, Ettore
AU - Kwaasi, Aaron
AU - Dunford, James
AU - Buccheri, Simona
AU - Caccamo, Nadia
AU - Dieli, Francesco
PY - 2008/11/13
Y1 - 2008/11/13
N2 - 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.
AB - 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.
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U2 - 10.1021/jm801003y
DO - 10.1021/jm801003y
M3 - Article
C2 - 18937434
AN - SCOPUS:56249146362
VL - 51
SP - 6800
EP - 6807
JO - Journal of Medicinal Chemistry
JF - Journal of Medicinal Chemistry
SN - 0022-2623
IS - 21
ER -