A Binuclear Gold(I) Complex with Mixed Bridging Diphosphine and Bis(N‐Heterocyclic Carbene) Ligands Shows Favorable Thiol Reactivity and Inhibits Tumor Growth and Angiogenesis In Vivo1. Issue 23 (11th April 2014)

• Record Type: Journal Article
• Authors: Zou, Taotao; Lum, Ching Tung; Lok, Chun‐Nam; To, Wai‐Pong; Low, Kam‐Hung; Che, Chi‐Ming
• Is Part Of: Angewandte Chemie international edition. Volume 53:Issue 23(2014)
• Page Start: 5810
• Page End: 5814
• Publication Date: 2014-04-11
• Subjects: Chemistry -- Periodicals; 540
• DOI: 10.1002/anie.201400142
• Languages: English
• ISSNs: 1433-7851

Abstract

<abstract abstract-type="main" xml:lang="en"> <title>Abstract</title> <p>In the design of anticancer gold(I) complexes with high in vivo efficacy, tuning the thiol reactivity to achieve stability towards blood thiols yet maintaining the thiol reactivity to target cellular thioredoxin reductase (TrxR) is of pivotal importance. Herein we describe a dinuclear gold(I) complex (<bold>1</bold>‐PF₆) utilizing a bridging bis(N‐heterocyclic carbene) ligand to attain thiol stability and a diphosphine ligand to keep appropriate thiol reactivity. Complex <bold>1</bold>‐PF₆ displays a favorable stability that allows it to inhibit TrxR activity without being attacked by blood thiols. In vivo studies reveal that <bold>1</bold>‐PF₆ significantly inhibits tumor growth in mice bearing HeLa xenograft and mice bearing highly aggressive mouse B16‐F10 melanoma. It inhibits angiogenesis in tumor models and inhibits sphere formation of cancer stem cells in vitro. Toxicology studies indicate that <bold>1</bold>‐PF₆ does not show systemic anaphylaxis on guinea pigs and localized irritation on rabbits.</p> </abstract>