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

• Published in: Bioorganic & medicinal chemistry 2017-10, Vol.25 (20), p.5452-5460
• Main Authors: Jürgens, Sophie, Scalcon, Valeria, Estrada-Ortiz, Natalia, Folda, Alessandra, Tonolo, Federica, Jandl, Christian, Browne, Duncan L., Rigobello, Maria Pia, Kühn, Fritz E., Casini, Angela
• Format: Article
• Language: English
• Subjects: Anticancer agents; Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Cell Line, Tumor; Cell Proliferation - drug effects; Cyclometalation; Dose-Response Relationship, Drug; Drug Screening Assays, Antitumor; Enzyme Inhibitors - chemical synthesis; Enzyme Inhibitors - chemistry; Enzyme Inhibitors - pharmacology; Gold(III) complexes; Humans; Molecular Structure; Organogold Compounds - chemical synthesis; Organogold Compounds - chemistry; Organogold Compounds - pharmacology; Oxidation-Reduction; Structure-Activity Relationship; Thiols; Thioredoxin reductase; Thioredoxin-Disulfide Reductase - antagonists & inhibitors; Thioredoxin-Disulfide Reductase - metabolism
• ISSN: 0968-0896; 1464-3391
• DOI: 10.1016/j.bmc.2017.08.001

[Display omitted] 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.