Back to Search
Start Over
Synthesis and preliminary pharmacological characterisation of a new class of nitrogen-containing bisphosphonates (N-BPs)
- Source :
- Bioorganic & Medicinal Chemistry. 18:2428-2438
- Publication Year :
- 2010
- Publisher :
- Elsevier BV, 2010.
-
Abstract
- A new series of bisphosphonates bearing either the nitrogen-containing NO-donor furoxan (1,2,5-oxadiazole 2-oxide) system or the related furazan (1,2,5-oxadiazole) in lateral chain has been developed. pKa values and affinity for hydroxyapatite were determined for all the compounds. The products were able to inhibit osteoclastogenesis on RAW 246.7 cells at 10 μM concentration. The most active compounds were further assayed on human PBMC cells and on rat microsomes. Unlike most nitrogen-containing bisphosphonates which target farnesyl pyrophosphate synthase, experimental and theoretical investigations suggest that the activity of our derivatives may be related to different mechanisms. The furoxan derivatives were also tested for their ability to relax rat aorta strips in view of their potential NO-dependent vasodilator properties.
- Subjects :
- Male
Models, Molecular
Magnetic Resonance Spectroscopy
Osteoclastogenesis
Nitrogen
Stereochemistry
Vasodilator Agents
Clinical Biochemistry
Farnesyl pyrophosphate
Pharmaceutical Science
Aorta, Thoracic
In Vitro Techniques
Furazan
Biochemistry
Bone and Bones
Chromatography, Affinity
Muscle, Smooth, Vascular
Nitric oxide
Mice
chemistry.chemical_compound
Osteogenesis
Drug Discovery
Animals
Humans
Nitric Oxide Donors
Rats, Wistar
Ibandronic Acid
Molecular Biology
Cells, Cultured
Bone Density Conservation Agents
Diphosphonates
ATP synthase
biology
Macrophages
Organic Chemistry
Furoxan
Bisphosphonates
Rats
Cardiovascular diseases
Durapatite
Farnesyl-Diphosphate Farnesyltransferase
chemistry
Bisphosphonates, Cardiovascular diseases, Nitric oxide, Osteoclastogenesis
Microsomes, Liver
Microsome
biology.protein
Molecular Medicine
nitric oxide
osteoclastogenesis
cardiovascular diseases
Subjects
Details
- ISSN :
- 09680896
- Volume :
- 18
- Database :
- OpenAIRE
- Journal :
- Bioorganic & Medicinal Chemistry
- Accession number :
- edsair.doi.dedup.....363962728925f7e93d81335be2417800