3-Hydroxyflavones vs. 3-hydroxyquinolinones: structure-activity relationships and stability studies on Ru-II(arene) anticancer complexes with biologically active ligands

Author(s): Andrea Kurzwernhart, Wolfgang Kandioller, Eva Anna Enyedy, Maria Novak, Michael Jakupec, Bernhard Keppler, Christian G. Hartinger
Abstract: Ru-II(eta(6)-arene) complexes, especially with bioactive ligands, are considered to be very promising compounds for anticancer drug design. We have shown recently that Ru-II(eta(6)-p-cymene) complexes with 3-hydroxyflavone ligands exhibit very high in vitro cytotoxic activities correlating with a strong inhibition of topoisomerase II alpha. In order to expand our knowledge about the structure-activity relationships and to determine the impact of lipophilicity of the arene ligand and of the hydrolysis rate on anticancer activity, a series of novel 3-hydroxyflavone derived Ru-II(eta(6)-arene) complexes were synthesised. Furthermore, the impact of the heteroatom in the bioactive ligand backbone was studied by comparing the cytotoxic activity of Ru-II(eta(6)-p-cymene) complexes of 3-hydroxyquinolinone ligands with that of their 3-hydroxyflavone analogues. To better understand the behaviour of these Ru-II complexes in aqueous solution, the stability constants and pK(a) values for complexes and the corresponding ligands were determined. Furthermore, the interaction with the DNA model 5'-GMP and with a series of amino acids was studied in order to identify potential biological target structures.
Organisation(s): Department of Inorganic Chemistry
External organisation(s): University of Szeged, University of Auckland
Journal: Dalton Transactions
Volume: 42
Pages: 6193-6202
No. of pages: 10
ISSN: 1477-9226
DOI: https://doi.org/10.1039/c2dt32206d
Publication date: 2013
Peer reviewed: Yes
Austrian Fields of Science 2012: 104003 Inorganic chemistry, 301207 Pharmaceutical chemistry
Portal url: https://ucrisportal.univie.ac.at/en/publications/e4976ce3-8be5-41b5-96e8-a3e072365aa1