Synthesis of NO-donor bisphosphonates and their in-vitro action on bone resorption

被引:24
作者
Lazzarato, L
Rolando, B
Lolli, ML
Tron, GC
Fruttero, R
Gasco, A
Deleide, G
Guenther, HL
机构
[1] Univ Turin, Dipartimento Sci & Tecnol Farm, I-10125 Turin, Italy
[2] Univ Piemonte, Dipartimento Sci Chim Alimentari Farmaceut & Farm, I-28100 Novara, Italy
[3] Nycomed Amersham Sorin Srl, I-13040 Saluggia, VC, Italy
[4] Univ Bern, Dept Clin Res, CH-3010 Bern, Switzerland
关键词
D O I
10.1021/jm040830d
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
A new class of bisphosphonates containing nitrooxy NO-donor functions has been developed. The products proved to display affinity for hydroxyapatite. Injection of Tc-99m-labeled derivatives 11 and 18 into male rats showed a preferential accumulation of the compounds in bone as compared to blood and muscles. The products were found to inhibit the differentiation of preosteoclasts to functional osteoclasts induced by receptor activator of NF-kappaB ligand (RANKL), through a prevalent NO-dependent mechanism.
引用
收藏
页码:1322 / 1329
页数:8
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