A Soluble Bis-Chelated Gold(I) Diphosphine Compound with Strong Anticancer Activity and Low Toxicity
Yanli Wang ‡, Minyu Liu †§, Ran Cao ‡, Wanbin Zhang †, Ming Yin †, Xuhua Xiao §, Quanhai Liu *§, and Niu Huang *‡
† School of Pharmacy, Shanghai Jiao Tong University, 800 Dong Chuan Road, Shanghai 200240, China
‡ National Institute of Biological Sciences, Beijing, 7 Science Park Road, Zhongguancun Life Science Park, Beijing 102206, China
§ Department of Pharmacology, Shanghai Institute of Pharmaceutical Industry, 1111 Zhong Shan Bei Yi Road, Shanghai 200437, China
J. Med. Chem., 2013, 56 (4), pp 1455–1466
DOI: 10.1021/jm3009822
Publication Date (Web): January 30, 2013


Gold-containing compounds have shown anticancer potential, but their clinical applications have been severely limited by poor stability and high toxicity in vivo. Here, we report a novel soluble bis-chelated gold(I)–diphosphine compound (GC20) with strong anticancer activity and low toxicity. GC20 shows strong antiproliferation potency against a broad spectrum of cancer cell lines including cisplatin-resistant cancer cells (IC50 ≈ 0.5 μM) and significantly reduces tumor growth in several tumor xenografts in mouse models at doses as low as 2 mg/kg. Studies of its mechanism revealed that GC20 specifically inhibits the enzymatic activity of thioredoxin reductase by binding to selenocysteine residue, without targeting other well-known selenol and thiol groups contained in biomolecules. Remarkably, in animal studies GC20 was shown to be well tolerated even at the high dose of 8 mg/kg. Our results strongly suggest that GC20 represents a promising candidate for the development of novel anticancer drugs.

[Epub ahead of print]