Synthesis of NO-donor bisphosphonates and their in-vitro action on bone resorption.
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.
Lazzarato
Loretta
L
Dipartimento di Scienza e Tecnologia del Farmaco, Università degli Studi di Torino, Via Pietro Giuria 9, 10125 Turin, Italy.
Rolando
Barbara
B
Lolli
Marco L
ML
Tron
Gian Cesare
GC
Fruttero
Roberta
R
Gasco
Alberto
A
Deleide
Guido
G
Guenther
Harald L
HL
D000818:Animals; D001862:Bone Resorption / Q000473:pathology*; D002352:Carrier Proteins / Q000494:pharmacology; D002454:Cell Differentiation; D002460:Cell Line; D004164:Diphosphonates / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D017886:Durapatite / Q000737:chemistry; D008297:Male; D008562:Membrane Glycoproteins / Q000494:pharmacology; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism; D020030:Nitric Oxide Donors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D010010:Osteoclasts / Q000166:cytology / Q000187:drug effects; D053245:RANK Ligand; D019275:Radiopharmaceuticals; D051381:Rats; D053246:Receptor Activator of Nuclear Factor-kappa B; D013670:Sodium Pertechnetate Tc 99m; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects; D013329:Structure-Activity Relationship; D014018:Tissue Distribution
D002352:Carrier Proteins; D004164:Diphosphonates; D008562:Membrane Glycoproteins; D016328:NF-kappa B; D020030:Nitric Oxide Donors; D053245:RANK Ligand; D019275:Radiopharmaceuticals; D053246:Receptor Activator of Nuclear Factor-kappa B; C505687:Tnfrsf11a protein, mouse; C505689:Tnfsf11 protein, mouse; D017886:Durapatite; D013670:Sodium Pertechnetate Tc 99m