Table of Contents
Metal-Based Drugs
Volume 3, Issue 1, Pages 31-47

The Effects of Amine-Carboxyborane Related Derivatives on UMR-106 Bone Metabolism

1Division of Pharmaceutics, School of Pharmacy, University of North Carolina, Chapel Hill 275559-7360, North Carolina, USA
2Division of Medicinal Chemistry and Natural Products, School of Pharmacy, University of North Carolina, Chapel Hill 275559-7360, North Carolina, USA
3Boron Biologicals, Inc., 620 Hutton St., Suite 104, Raleigh 27606, North Carolina, USA

Received 7 November 1995; Accepted 7 December 1995

Copyright © 1996 Hindawi Publishing Corporation. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


The amine-carboxyboranes and related derivatives have been shown to be potent anti-inflammatory and anti-osteoporosis agents. Their action in part appears to be mediated by the modulation of cytokines, e.g. TNFα or IL-1. Previous studies have demonstrated that LPS induced macrophages release of TNFα maximally at 60 to 90 min. and IL-1 from 5 to 8 hr. The amine-carboxyboranes reduced significantly the release of these cytokines but also blocked TNFα high affinity binding to UMR-106 receptor at 90 min. at 10 μM, and IL-1 high affinity binding at 5 hr. at 12.5 μM. In addition, the agents suppressed IL-8 binding to CHO K1 high affinity receptor at 24 hr. at 50 μM and IL-2 binding to HuT-8 receptors at 25 μM at 90 min. and 5 hr. Correlation of metabolic events associated with osteoporosis showed that at 90 min., when TNFα receptor binding was reduced by the agents, calcium uptake into UMR-106 cells was reduced at 10 μM as well as the acid and alkaline phosphatases, and the prostaglandin cyclo-oxygenase activities and adhesion of leukocytes and macrophages to UMR-106 cell monolayers. At 5hr. when the agents reduced IL-1 binding to UMR-106 receptors, calcitonin and 1,25-dihydrovitamin D3 binding was reduced by the agents as was acid and alkaline phosphatase, and 5′-lipoxygenase activities and white blood cell adhesion. At this time calcium uptake and proline incorporation was increased significantly by the agents. At later times e.g. 18-48 hr. calcium uptake was still increased, and NAG activity was inhibited in the presence of the agents. These effects may be related more to the inhibition of other cytokine receptor binding, e.g. IL-8. Thus, many of the observed metabolic effects of amine-carboxyboranes as antiosteoporosis agents can be correlated with their inhibition of cytokine high affinity binding to target cell receptors.