The anti-osteoporotic activity of amine-carboxyboranes in rodents.
Amine-carboxyboranes have been shown to prevent osteoporosis and loss of bone mass in rodents. In vitro studies using CF1 mouse pup calvaria and rat UMR-106 osteosarcoma cells showed that amine-carboxyborane derivatives reduced significantly the loss of intracellular calcium into the growth medium from 10(-4) to 10(-8) M over 48 hours. Amine-carboxyborane derivatives were more effective than calcitonin or simple boron salts. Calcium incorporation into these cells and proline incorporation into collagen was accelerated in the presence of amine carboxyboranes. The amine-carboxyborane derivatives effectively inhibited lysosomal and proteolytic enzymes as well as activities of serine elastase, prostaglandin cyclooxygenase, and 5'-lipoxygenase in mouse macrophages, human PMNs, leukocytes and Be Sal cells. IC50 values were in the range of 10(-6) M. In lactating ovariectomized female rats after administered amine-carboxyboranes for 14 days at 8 mg/kg/day orally, the femur and humerus showed increased volume, weight, density and ash weight. Serum calcium levels were elevated significantly with minimum reductions on serum inorganic phosphate levels. Femur calcium levels were elevated after treatment with amine-carboxyborane derivatives, but not with etidronate. Humerus total lipids after 14 days were slightly elevated probably due to increased levels of triglycerides and phospholipids.
Rajendran
K G
KG
Division of Medicinal Chemistry and Natural Products, School of Pharmacy, University of North Carolina, Chapel Hill 27599-7360, USA.
Chen
S Y
SY
Sood
A
A
Spielvogel
B F
BF
Hall
I H
IH
D000818:Animals; D001859:Bone Neoplasms / Q000378:metabolism / Q000473:pathology; D001880:Boranes / Q000494:pharmacology / Q000627:therapeutic use*; D002118:Calcium / Q000032:analysis; D005260:Female; D006909:Hydroxyproline / Q000032:analysis; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D010024:Osteoporosis / Q000188:drug therapy* / Q000378:metabolism; D012516:Osteosarcoma / Q000378:metabolism / Q000473:pathology; D010758:Phosphorus / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D012886:Skull / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D014407:Tumor Cells, Cultured / Q000187:drug effects
D001880:Boranes; D010758:Phosphorus; D006909:Hydroxyproline; D002118:Calcium