Metabolism and protein binding behavior of flavonoid-derived metal complexes in biological systems

Supervisor: Bernhard Keppler, Institute of Inorganic Chemistry

Student: Gerlinde Grabmann

Platinum-based chemotherapeutics are among the most successful antitumor agents [1], but exhibit low selectivity and cause side effects or are prone to resistance. In order to overcome these problems, we have extended our synthetic program from pyr(id)one-derived Ru complexes to modified flavones. Flavones are known to have beneficial effects against atherosclerosis, osteoporosis, diabetes mellitus and certain types of cancer [2], the latter being attributed to the inhibition of kinases, but also interference with topoisomerase and selective estrogen receptor mediator function was observed [3-5]. Within this project, ruthenium-arene compounds of hydroxyflavones will be included in chemical and biological assays in order to identify their molecular modes of action. These will include extensive studies on their behavior in biologically relevant media and on their biophysical properties. Modern analytical methodology such as capillary electrophoresis (CE), HPLC, mass spectrometry (MS) and NMR will be applied and new assays will be established in cooperation with other members of the consortium.

1. Galanski M, Arion VB, Jakupec MA, Keppler BK (2003) Curr. Pharm. Des. 9:2078-2089

2. Cermak R (2008) Expert Opin. Drug Metab. Toxicol. 4:17-35

3. Sausville EA (2005) Curr. Top. Med. Chem. 5:1109-1117

4. Das BB, Sen N, Roy A, Dasgupta SB, Ganguly A, Mohanta BC, Dinda B, Majumder HK (2006) Nucleic Acids Res. 34:1121-1132

5. Winkelmann I, Naessl A-M, Daniel H, Wenzel U (2008) Int. J. Cancer 122:2223-2232