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Organometallic Antitumour Agents with Alternative Modes of Action

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Medicinal Organometallic Chemistry

Part of the book series: Topics in Organometallic Chemistry ((TOPORGAN,volume 32))

Abstract

The therapeutic index of drugs that target DNA, a ubiquitous target present in nearly all cells, is low. Nevertheless, DNA has remained the primary target for medicinal chemists developing metal-based anticancer drugs, although DNA has been essentially abandoned in favour of non-genomic targets by medicinal chemists developing organic drugs. A number of organometallic drugs that target proteins/enzymes have been developed and these compounds, based on ruthenium, osmium and gold, are described in this chapter. Targets include cathepsin B, thioredoxin reductases, multidrug resistance protein (Pgp), glutathione S-transferases and kinases. It is found that compounds that inhibit these various targets are active against metastatic tumours, or tumours that are resistant to classical DNA damaging agents such as cisplatin, and therefore offer considerable potential in clinical applications.

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Acknowledgments

Funding from the Swiss National Science Foundation, Swiss League Contre Le Cancer, Swiss State Secretariat for Education and Research, European Union, German Academic Exchange Programme, Austrian Science Fund and Eclosion are gratefully acknowledged. We would also like to thank our on-going collaborators, including Gianni Sava and Alberta Bergamo (Trieste), Bernhard Keppler (Vienna), Georg Süss-Fink and Bruno Therrien (Neuchâtel), and Luigi Messori (Florence), and fellow co-workers past and present whose names may be found in the references.

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  1. Ecole Polytechnique Fédérale de Lausanne (EPFL), Institut des Sciences et Ingénierie Chimiques, Lausanne, CH-1015, Switzerland

    Angela Casini, Christian G. Hartinger, Alexey A. Nazarov & Paul J. Dyson

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  1. Angela Casini
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  2. Christian G. Hartinger
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  3. Alexey A. Nazarov
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  4. Paul J. Dyson
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Correspondence to Paul J. Dyson .

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  1. Chimie de Paris (ENSCP), Ecole Nationale Superieure de, rue Pierre et Marie Curie 11, Paris CX 05, 75231, France

    Gérard Jaouen

  2. LS für Anorganische Chemie I -, Bioanorganische Chemie, Universität Bochum, Universitätsstr. 150, Bochum, 44801, Germany

    Nils Metzler-Nolte

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Casini, A., Hartinger, C.G., Nazarov, A.A., Dyson, P.J. (2010). Organometallic Antitumour Agents with Alternative Modes of Action. In: Jaouen, G., Metzler-Nolte, N. (eds) Medicinal Organometallic Chemistry. Topics in Organometallic Chemistry, vol 32. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-13185-1_3

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