Book of Abstracts - Ruhr-Universität Bochum
Book of Abstracts - Ruhr-Universität Bochum
Book of Abstracts - Ruhr-Universität Bochum
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OP-2<br />
ISBOMC `10 5.7 – 9.7. 2010 <strong>Ruhr</strong>-<strong>Universität</strong> <strong>Bochum</strong><br />
Bioorganometallic Solutions for the Design<br />
<strong>of</strong> Novel Gold Anticancer Metallodrugs<br />
Ingo Ott, *a Riccardo Rubbiani, a Igor Kitanovic, b Hamed Alborzinia, b Suzan Can, b Stefan Wölfl, b<br />
Liliane A. Onambele, c Aram Prokop c<br />
a Technische <strong>Universität</strong> Braunschweig, Institute <strong>of</strong> Pharmaceutical Chemistry, Beethovenstr. 55,<br />
38106, Braunschweig, Germany, b Ruprecht-Karls-<strong>Universität</strong> Heidelberg, Institut für Pharmazie und<br />
Molekulare Biotechnologie, Im Neuenheimer Feld 364, 69120 Heidelberg, Germany c) Kliniken der<br />
Stadt Köln GmbH; E-mail: ingo.ott@tu-bs.de<br />
Motivated by the success <strong>of</strong> gold species in the treatment <strong>of</strong> rheumatoid arthritis and by the promising<br />
outcome <strong>of</strong> several preclinical studies increasing efforts have been made to develop gold complexes<br />
also for the use in cancer chemotherapy. Concerning the mode <strong>of</strong> drug action thioredoxin reductase<br />
(TrxR), an enzyme closely related to glutathione reductase (GR), is nowadays considered as the most<br />
relevant molecular target based on the high selectivity <strong>of</strong> gold species for this enzyme and its<br />
substantial involvement in tumor growth and progression. 1-3<br />
Here we wish to present our most recent results obtained with gold(I) bioorganometallics featuring Nheterocyclic<br />
carbene (NHC) derived ligands (see the figure below for a relevant example) in<br />
comparison to relevant non organometallic gold(I) phosphine complexes such as auran<strong>of</strong>in.<br />
Promising antiproliferative effects were noted in MCF-7 breast adenocarcinoma as well as HT-29<br />
colon carcinoma cells and the target compounds were found to be strong and selective inhibitors <strong>of</strong><br />
TrxR with an increased stability against glutathione. More detailed studies on a selected gold(I) NHC<br />
complex revealed a strong induction <strong>of</strong> apoptosis and reactive oxygene species (ROS) formation,<br />
antimitochondrial properties, as well as distinct effects on cellular metabolism.<br />
References<br />
N<br />
N<br />
18<br />
Au Cl<br />
Figure: example for a bioactive gold(I) NHC complex<br />
1. I. Ott, Coord. Chem. Rev. 2009, 253, 1670-1681.<br />
2. A. Bindoli, M. P. Rigobello, G. Scutari, C. Gabbiani, A. Casini, L. Messori, Coord. Chem. Rev.<br />
2009, 253, 1692-1707.<br />
3. P. J. Barnard, S. J. Berners-Price, Coord. Chem. Rev. 2007, 251, 1889-1902.
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