Lanthanide pyrone and pyridinone complexes for the treatment of bone density disorders

INOR 521

Cheri A. Barta, cbarta@chem.ubc.ca1, Yasmin J. Mawani, ymawani@chem.ubc.ca2, Kristina Sachs-Barrabel, sachs@interchange.ubc.ca1, Katherine H. Thompson, kthompso@chem.ubc.ca2, Kishor M. Wasan, kwasan@interchange.ubc.ca1, and Chris Orvig, orvig@chem.ubc.ca2. (1) Faculty of Pharmaceutical Sciences, University of British Columbia, 2146 East Mall, Vancouver, BC V6T 1Z3, Canada, (2) Department of Chemistry, University of British Columbia, 2035 Main Mall, Vancouver, BC V6T 1Z1, Canada
Lanthanide ions, Ln(III), are known functional mimics of Ca(II) ions and have been shown to affect the bone remodeling cycle. Exploiting this disruption to the bone remodeling cycle has potential for the treatment of bone density disorders, such as osteoporosis. Lanthanum carbonate has been proposed as a potential preventative measure for post-menopausal osteoporosis; however, known negative side effects (e.g. gastrointestinal upset) have obviated its development. In an effort to find new orally available active agents for bone density disorders that circumvent the problems associated with lanthanum carbonate, our group is investigating a series of lanthanide containing complexes incorporating small, non-toxic, bidentate pyrone and pyridinone ligands (LnL3, Ln = La, Eu, Gd, Tb, Yb, L = 3-hydroxy-2-methyl-4-pyrone, 3-hydroxy-2-ethyl-4-pyrone, 3-hydroxy-1,2-dimethyl-4-pyridinone and 3-hydroxy-2-methyl-4(1H)-pyridinone). The synthesis and characterization of the complexes will be discussed. The preliminary biological analyses including cytotoxicity, cell uptake and bidirectional transport studies in Caco-2 cells and in vitro hydroxyapatite binding studies will also be shown.

Chemistry of Lanthanides and Actinides
7:00 PM-9:00 PM, Tuesday, August 19, 2008 Pennsylvania Convention Center -- Hall C, Poster

8:00 PM-10:00 PM, Monday, August 18, 2008 Pennsylvania Convention Center -- Hall C, Sci-Mix

Division of Inorganic Chemistry

The 236th ACS National Meeting, Philadelphia, PA, August 17-21, 2008