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Therapeutic Gold Compounds
S. Berners-Price, P. Barnard
Published 2014 · Chemistry
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Whilst the application of gold in medicine is traceable for several thousand years and gold drugs have been used clinically to treat rheumatoid arthritis since the last century, there has been unprecedented recent interest in the design of gold compounds (both AuI and AuIII) to treat a wide range of different diseases. The stimulus for this research has been recognition of the unique chemistry of gold (high affinity for cysteine and selenocysteine residues) combined with the emergence of a variety of thiol and selenol protein drug targets, whose dysfunction in cells can cause or contribute to a variety of human diseases. In this Chapter we focus on the design of gold-based drugs and the role of ligands in controlling the reactivity of the metal centre, or in influencing cellular uptake and modulation of biological activity. We pay special attention to the design of AuI phosphine and N-heterocyclic compounds as antiarthritic and/or anticancer agents and their specific inhibition of enzyme targets such as thioredoxin reductase, the cathepsins and protein tyrosine phosphatases, as well as the role of ligand design in fine-tuning the reactivity of AuIII antitumour agents. We highlight also the opportunity to design gold drugs to target the emerging parasite drug targets in trypanosomes (African sleeping sickness, Chagas' disease and leishmaniasis), malaria-causing plasmodia and schistosomiasis, as well as exciting recent developments in the design of gold-based anticancer peptidomimetics for targeted drug delivery.
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