Book of Abstracts - Ruhr-Universität Bochum

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OP-1 ISBOMC `10 5.7 – 9.7. 2010 Ruhr-Universität Bochum Bioorganometallics in Medicinal Inorganic Chemistry Chris Orvig *a a Medicinal Inorganic Chemistry Group, Department of Chemistry, University of British Columbia, 2036 Main Mall, Vancouver, BC V6T 1Z1, Canada. E-mail: orvig@chem.ubc.ca Bioorganometallic chemistry was an oxymoron in the 1970s when Pt compounds emerged for cancer chemotherapy and Tc compounds took flight as nuclear medicine imaging agents. At that time, the speaker fastidiously avoided working with technetium carbonyl compounds when he was a graduate student! Now, thanks to the effort of this community, bioorganometallic chemistry plays a valuable role to the larger fields of medicinal inorganic chemistry and medicinal chemistry. Efforts in the speaker's labs to develop organometallic compounds for therapy and diagnosis will be outlined, focussing on recent results in antimalarial and imaging applications. 17
OP-2 ISBOMC `10 5.7 – 9.7. 2010 Ruhr-Universität Bochum Bioorganometallic Solutions for the Design of Novel Gold Anticancer Metallodrugs Ingo Ott, *a Riccardo Rubbiani, a Igor Kitanovic, b Hamed Alborzinia, b Suzan Can, b Stefan Wölfl, b Liliane A. Onambele, c Aram Prokop c a Technische Universität Braunschweig, Institute of Pharmaceutical Chemistry, Beethovenstr. 55, 38106, Braunschweig, Germany, b Ruprecht-Karls-Universität Heidelberg, Institut für Pharmazie und Molekulare Biotechnologie, Im Neuenheimer Feld 364, 69120 Heidelberg, Germany c) Kliniken der Stadt Köln GmbH; E-mail: ingo.ott@tu-bs.de Motivated by the success of gold species in the treatment of rheumatoid arthritis and by the promising outcome of several preclinical studies increasing efforts have been made to develop gold complexes also for the use in cancer chemotherapy. Concerning the mode of drug action thioredoxin reductase (TrxR), an enzyme closely related to glutathione reductase (GR), is nowadays considered as the most relevant molecular target based on the high selectivity of gold species for this enzyme and its substantial involvement in tumor growth and progression. 1-3 Here we wish to present our most recent results obtained with gold(I) bioorganometallics featuring Nheterocyclic carbene (NHC) derived ligands (see the figure below for a relevant example) in comparison to relevant non organometallic gold(I) phosphine complexes such as auranofin. Promising antiproliferative effects were noted in MCF-7 breast adenocarcinoma as well as HT-29 colon carcinoma cells and the target compounds were found to be strong and selective inhibitors of TrxR with an increased stability against glutathione. More detailed studies on a selected gold(I) NHC complex revealed a strong induction of apoptosis and reactive oxygene species (ROS) formation, antimitochondrial properties, as well as distinct effects on cellular metabolism. References N N 18 Au Cl Figure: example for a bioactive gold(I) NHC complex 1. I. Ott, Coord. Chem. Rev. 2009, 253, 1670-1681. 2. A. Bindoli, M. P. Rigobello, G. Scutari, C. Gabbiani, A. Casini, L. Messori, Coord. Chem. Rev. 2009, 253, 1692-1707. 3. P. J. Barnard, S. J. Berners-Price, Coord. Chem. Rev. 2007, 251, 1889-1902.
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Sergey Abramkin Universität Wien,
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Tensim Dallagi ENSCP, France t.dall
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Prof. Dr. Toshikazu Hirao Osaka Uni
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Obiora Augustine Orakwue Hyqid Nige
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Book of Abstracts - Ruhr-Universität Bochum

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