Flavonoid-Based Organometallics with Different Metal Centers - Investigations of the Effects on Reactivity and Cytotoxicity

Author(s)

Andrea Kurzwernhart, Stephan Mokesch, Erik Klapproth, Mahsa Sadat Adib Razavi, Michael A. Jakupec, Christian G. Hartinger, Wolfgang Kandioller, Bernhard K. Keppler

Abstract

Flavonol-derived Os

^II(cym) and Rh

^III-Cp∗ complexes were synthesized and the impact of the metal center on aqueous stability, reactivity toward biomolecules, and cytotoxic activity was compared to Ru

^II analogs. The Rh

^III complexes were the most stable to ligand release in aqueous solution and showed the highest preference for ubiquitin binding. Investigations on the reactivity toward nucleoside triphosphates revealed the clear affinity of Rh

^III to 5′-dATP, whereas Ru

^II and Os

^II prefer binding to 5′-dGTP. Simultaneous incubation with amino acids and nucleoside triphosphates reveals the preference toward amino acids, indicating that binding to proteins might be a key step in the mechanism of action of this compound class. The complexes exhibit in vitro anticancer activities in the high nM to low μM range, confirming the flavonol scaffold as a promising O,O-chelating ligand system for the development of anticancer active organometallics. The effects of metal center variation of flavonoid-based organometallic complexes on aqueous stability, reactivity toward biomolecules, and cytotoxicity were investigated.

Organisation(s)

Department of Inorganic Chemistry

External organisation(s)

University of Auckland

Journal

European Journal of Inorganic Chemistry

Volume

2016

Pages

240-246

No. of pages

ISSN

1434-1948

DOI

https://doi.org/10.1002/ejic.201501020

Publication date

01-2016

Peer reviewed

Yes

Austrian Fields of Science 2012

104003 Inorganic chemistry

Keywords

ASJC Scopus subject areas

Inorganic Chemistry

Sustainable Development Goals

SDG 3 - Good Health and Well-being

Portal url

https://ucrisportal.univie.ac.at/en/publications/57b4d8cf-f2e6-4126-8bdf-24888846742a