A soluble bis-chelated gold(I) diphosphine compound with strong anticancer activity and low toxicity.

Abstract	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.
Authors	Yanli Wang, Minyu Liu, Ran Cao, Wanbin Zhang, Ming Yin, Xuhua Xiao, Quanhai Liu, Niu Huang
Journal	Journal of medicinal chemistry (J Med Chem) Vol. 56 Issue 4 Pg. 1455-66 (Feb 28 2013) ISSN: 1520-4804 [Electronic] United States
PMID	23362983 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References	Antineoplastic Agents Coordination Complexes Phosphines Gold Thioredoxin-Disulfide Reductase Glutathione Cisplatin
Topics	Animals Antineoplastic Agents (chemical synthesis, chemistry, pharmacology) Cell Line, Tumor Cisplatin (pharmacology) Coordination Complexes (chemical synthesis, chemistry, pharmacology) Drug Resistance, Neoplasm Drug Screening Assays, Antitumor Female G1 Phase (drug effects) Glutathione (metabolism) Gold Humans Lethal Dose 50 Mice Mice, Inbred ICR Mice, Nude Neoplasm Transplantation Phosphines (chemistry) Rats Rats, Sprague-Dawley Resting Phase, Cell Cycle (drug effects) Structure-Activity Relationship Thioredoxin-Disulfide Reductase (antagonists & inhibitors) Transplantation, Heterologous

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