Exploring the C^N^C theme: Synthesis and biological properties of tridentate cyclometalated gold(III) complexes

Sophie Jürgens; Valeria Scalcon; Natalia Estrada-Ortiz; Alessandra Folda; Federica Tonolo; Christian Jandl; Duncan L Browne; Maria Pia Rigobello; Fritz E Kühn; Angela Casini

doi:10.1016/j.bmc.2017.08.001

Exploring the C^N^C theme: Synthesis and biological properties of tridentate cyclometalated gold(III) complexes

Bioorg Med Chem. 2017 Oct 15;25(20):5452-5460. doi: 10.1016/j.bmc.2017.08.001. Epub 2017 Aug 9.

Affiliations

¹ Molecular Catalysis, Catalysis Research Centre and Department of Chemistry, Technische Universität München, Lichtenbergstr. 4, 85747 Garching bei München, Germany; School of Chemistry, Cardiff University, Park Place, Cardiff CF10 3AT, United Kingdom.
² Dept. of Biomedical Sciences, University of Padova, via Ugo Bassi 58/b, 35131 Padova, Italy.
³ Dept. Pharmacokinetics, Toxicology and Targeting, University of Groningen, A. Deusinglaan 1, 9713 AV Groningen, The Netherlands.
⁴ Molecular Catalysis, Catalysis Research Centre and Department of Chemistry, Technische Universität München, Lichtenbergstr. 4, 85747 Garching bei München, Germany.
⁵ School of Chemistry, Cardiff University, Park Place, Cardiff CF10 3AT, United Kingdom.
⁶ Molecular Catalysis, Catalysis Research Centre and Department of Chemistry, Technische Universität München, Lichtenbergstr. 4, 85747 Garching bei München, Germany. Electronic address: fritz.kuehn@ch.tum.de.
⁷ School of Chemistry, Cardiff University, Park Place, Cardiff CF10 3AT, United Kingdom; Dept. Pharmacokinetics, Toxicology and Targeting, University of Groningen, A. Deusinglaan 1, 9713 AV Groningen, The Netherlands; Institute of Advanced Study, Technische Universität München, Lichtenbergstr. 2a, 85748 Garching bei München, Germany. Electronic address: casinia@cardiff.ac.uk.

PMID: 28823538
DOI: 10.1016/j.bmc.2017.08.001

Abstract

A family of cyclometalated Au(III) complexes featuring a tridentate C^N^C scaffold has been synthesized and characterized. Microwave assisted synthesis of the ligands has also been exploited and optimized. The biological properties of the thus formed compounds have been studied in cancer cells and demonstrate generally moderate antiproliferative effects. Initial mechanistic insights have also been gained on the gold complex [Au(C^N^C)(GluS)] (3), and support the idea that the thioredoxin system may be a target for this family of compounds together with other relevant intracellular thiol-containing molecules.

Keywords: Anticancer agents; Cyclometalation; Gold(III) complexes; Thiols; Thioredoxin reductase.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Antineoplastic Agents / chemical synthesis
Antineoplastic Agents / chemistry
Antineoplastic Agents / pharmacology*
Cell Line, Tumor
Cell Proliferation / drug effects
Dose-Response Relationship, Drug
Drug Screening Assays, Antitumor
Enzyme Inhibitors / chemical synthesis
Enzyme Inhibitors / chemistry
Enzyme Inhibitors / pharmacology*
Humans
Molecular Structure
Organogold Compounds / chemical synthesis
Organogold Compounds / chemistry
Organogold Compounds / pharmacology*
Oxidation-Reduction
Structure-Activity Relationship
Thioredoxin-Disulfide Reductase / antagonists & inhibitors
Thioredoxin-Disulfide Reductase / metabolism

Substances

Antineoplastic Agents
Enzyme Inhibitors
Organogold Compounds
Thioredoxin-Disulfide Reductase