Organometallic Osmium Arene Complexes with Potent Cancer Cell Cytotoxicity
Journal of Medicinal Chemistry2010Vol. 53(22), pp. 8192–8196
Citations Over TimeTop 10% of 2010 papers
Ying Fu, Abraha Habtemariam, Ana M. Pizarro, Sabine van Rijt, David J. Healey, Patricia A. Cooper, Steven D. Shnyder, Guy J. Clarkson, Peter J. Sadler
Abstract
Iodido osmium(II) complexes [Os(η(6)-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., IC(50) = 140 nM for [Os(η(6)-bip)(azpy-NMe(2))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.
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