Design, Synthesis, and Biological Evaluation of Novel Aminobisphosphonates Possessing an in Vivo Antitumor Activity Through a γδ-T Lymphocytes-Mediated Activation Mechanism

被引：69

作者：

Simoni, Danicle ^{[8
]}

Gebbia, Nicola ^{[1
]}

Invidiata, Francesco Paolo ^{[2
]}

Eleopra, Marco ^{[8
]}

Marchetti, Paolo ^{[8
]}

Rondanin, Riccardo ^{[8
]}

Baruchello, Riccardo ^{[8
]}

Provera, Stefano ^{[3
]}

Marchicro, Carla ^{[3
]}

Tolomeo, Manho ^{[4
]}

Marinelli, Luciana ^{[5
]}

Limongelli, Vittorio ^{[5
]}

Novellino, Ettore ^{[5
]}

Kwaasi, Aaron ^{[6
]}

Dunford, James ^{[6
]}

Buccheri, Siniona ^{[7
]}

Caccamo, Nadia ^{[7
]}

Dieli, Francesco ^{[7
]}

机构：

[1] CoRiBiA, Palermo, Italy

[2] Univ Palermo, Dipartimento Farmacochim Tossicol & Biol, I-90133 Palermo, Italy

[3] GlaxoSmithKline, Med Res Ctr, Verona, Italy

[4] Univ Palermo, Div Ematol Serv AIDS Policlin, Palermo, Italy

[5] Univ Naples Federico II, Dipartimento Chim Farmaceut & Tossicol, I-80131 Naples, Italy

[6] Univ Oxford, Nuffield Dept Orthopaed Surg, Nuffield Orthopaed Ctr, Botnar Res Ctr,Inst Musculoskeletal Sci, Oxford OX3 7LD, England

[7] Univ Palermo, Dipartimento Biopatol & Metodol Biomed, Palermo, Italy

[8] Univ Ferrara, Dipartimento Sci Farmaceut, I-44100 Ferrara, Italy

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2008年 / 51卷 / 21期

关键词：

D O I：

10.1021/jm801003y

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

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

引用

页码：6800 / 6807

页数：8

共 42 条

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