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Organometallic osmium arene complexes with potent cancer cell cytotoxicity.

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.
AuthorsYing Fu, Abraha Habtemariam, Ana M Pizarro, Sabine H van Rijt, David J Healey, Patricia A Cooper, Steven D Shnyder, Guy J Clarkson, Peter J Sadler
JournalJournal of medicinal chemistry (J Med Chem) Vol. 53 Issue 22 Pg. 8192-6 (Nov 25 2010) ISSN: 1520-4804 [Electronic] United States
PMID20977192 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Antineoplastic Agents
  • Azo Compounds
  • Biphenyl Compounds
  • Coordination Complexes
  • Cymenes
  • Free Radical Scavengers
  • Monoterpenes
  • Pyridines
  • Reactive Oxygen Species
  • 4-cymene
  • Osmium
  • Glutathione
  • Acetylcysteine
Topics
  • Acetylcysteine (pharmacology)
  • Antineoplastic Agents (chemical synthesis, chemistry, pharmacology)
  • Azo Compounds (chemical synthesis, chemistry, pharmacology)
  • Biphenyl Compounds (chemical synthesis, chemistry, pharmacology)
  • Cell Line, Tumor
  • Coordination Complexes (chemical synthesis, chemistry, pharmacology)
  • Crystallography, X-Ray
  • Cymenes
  • Drug Screening Assays, Antitumor
  • Drug Stability
  • Free Radical Scavengers (pharmacology)
  • Glutathione (metabolism)
  • Humans
  • Hydrolysis
  • Models, Molecular
  • Molecular Structure
  • Monoterpenes (chemical synthesis, chemistry, pharmacology)
  • Osmium
  • Pyridines (chemical synthesis, chemistry, pharmacology)
  • Reactive Oxygen Species (metabolism)
  • Structure-Activity Relationship

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