Organometallic Osmium Arene Complexes with Potent Cancer Cell Cytotoxicity

• Published in: Journal of medicinal chemistry Vol. 53; no. 22; pp. 8192 - 8196
• Main Authors: Fu, Ying, Habtemariam, Abraha, Pizarro, Ana M, van Rijt, Sabine H, Healey, David J, Cooper, Patricia A, Shnyder, Steven D, Clarkson, Guy J, Sadler, Peter J
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 25.11.2010
• Subjects: Acetylcysteine - pharmacology; Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Azo Compounds - chemical synthesis; Azo Compounds - chemistry; Azo Compounds - pharmacology; Biphenyl Compounds - chemical synthesis; Biphenyl Compounds - chemistry; Biphenyl Compounds - pharmacology; Cell Line, Tumor; Coordination Complexes - chemical synthesis; Coordination Complexes - chemistry; Coordination Complexes - pharmacology; Crystallography, X-Ray; Drug Screening Assays, Antitumor; Drug Stability; Free Radical Scavengers - pharmacology; Glutathione - metabolism; Humans; Hydrolysis; Models, Molecular; Molecular Structure; Monoterpenes - chemical synthesis; Monoterpenes - chemistry; Monoterpenes - pharmacology; Osmium; Pyridines - chemical synthesis; Pyridines - chemistry; Pyridines - pharmacology; Reactive Oxygen Species - metabolism; Structure-Activity Relationship
• ISSN: 0022-2623; 1520-4804; 1520-4804
• DOI: 10.1021/jm100560f

Iodido osmium(II) complexes [Os(η6-arene)(XY)I]+ (XY = p-hydroxy or p-dimethylaminophenylazopyridine, arene = p-cymene or biphenyl) are potently cytotoxic at nanomolar concentrations toward a panel of human cancer cell lines; e.g., IC50 = 140 nM for [Os(η6-bip)(azpy-NMe2)I]+ toward A2780 ovarian cancer cells. They exhibit low toxicity and negligible deleterious effects in a colon cancer xenograft model, giving rise to the possibility of a broad therapeutic window. The most active complexes are stable and inert toward aquation. Their cytotoxic activity appears to involve redox mechanisms.