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

J Med Chem. 2005 Mar 10;48(5):1322-9. doi: 10.1021/jm040830d.

Abstract

A new class of bisphosphonates containing nitrooxy NO-donor functions has been developed. The products proved to display affinity for hydroxyapatite. Injection of (99m)Tc-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 pre-osteoclasts to functional osteoclasts induced by receptor activator of NF-kappaB ligand (RANKL), through a prevalent NO-dependent mechanism.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bone Resorption / pathology*
  • Carrier Proteins / pharmacology
  • Cell Differentiation
  • Cell Line
  • Diphosphonates / chemical synthesis*
  • Diphosphonates / chemistry
  • Diphosphonates / pharmacology
  • Durapatite / chemistry
  • Male
  • Membrane Glycoproteins / pharmacology
  • Mice
  • NF-kappa B / metabolism
  • Nitric Oxide Donors / chemical synthesis*
  • Nitric Oxide Donors / chemistry
  • Nitric Oxide Donors / pharmacology
  • Osteoclasts / cytology
  • Osteoclasts / drug effects
  • RANK Ligand
  • Radiopharmaceuticals
  • Rats
  • Receptor Activator of Nuclear Factor-kappa B
  • Sodium Pertechnetate Tc 99m
  • Stem Cells / cytology
  • Stem Cells / drug effects
  • Structure-Activity Relationship
  • Tissue Distribution

Substances

  • Carrier Proteins
  • Diphosphonates
  • Membrane Glycoproteins
  • NF-kappa B
  • Nitric Oxide Donors
  • RANK Ligand
  • Radiopharmaceuticals
  • Receptor Activator of Nuclear Factor-kappa B
  • Tnfrsf11a protein, mouse
  • Tnfsf11 protein, mouse
  • Durapatite
  • Sodium Pertechnetate Tc 99m