Book of Abstracts - Ruhr-Universität Bochum

OP-18
ISBOMC `10 5.7 – 9.7. 2010 Ruhr-Universität Bochum
Organometallic Anticancer Drugs: From Simple Structures to Rational Drug
Design Based on a Mechanistic Approach
Paul J. Dyson
Institut des Sciences et Ingénierie Chimiques, Ecole Polytechnique Fédérale de Lausanne (EPFL), CH
1015 Lausanne, Switzerland. E-mail: paul.dyson@epfl.ch
Organometallic chemistry has a strong tradition in the rational synthesis of compounds with
specific functions, whatever the nature of the required function. But how is rational synthesis
of organometallic pharmaceutical compounds currently achieved? The first part of the
presentation will discuss the relevant issues by considering examples from the literature as
well as from my own laboratory. 1 The presentation then continue with a focus on
organometallic compounds based on the ruthenium(II)-arene unit developed in my laboratory
that exhibit excellent in vivo anticancer activity and overcome certain limitations of presently
used drugs. 2 The elements of the drug design process and the relevant known drug targets will
be discussed. It will be shown that ligands with specific functions can be introduced into the
drug structure in order to endow the compound with specific properties allowing the metal to
perform a more classical role.
One of the overriding features of the compounds discussed during the presentation is that
targets other than DNA, i.e. enzyme and protein targets, are crucial for metal drugs, especially
for the ruthenium(II)-arene drugs emanating from my laboratory, and evidence to support this
notion will be provided.
References
1. C. G. Hartinger, P. J. Dyson, Chem. Soc. Rev., 2009, 38, 391–401.
2. W. H. Ang, L. J. Parker, A. De Luca, L. Juillerat-Jeanneret, C. J. Morton, M. Lo Bello, M. W.
Parker, P. J. Dyson, Angew. Chem. Int. Ed., 2009, 48, 3854–3857.
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