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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Authors | Ying 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 |
Journal | Journal of medicinal chemistry
(J Med Chem)
Vol. 53
Issue 22
Pg. 8192-6
(Nov 25 2010)
ISSN: 1520-4804 [Electronic] United States |
PMID | 20977192
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Antineoplastic Agents
- Azo Compounds
- Biphenyl Compounds
- Coordination Complexes
- Cymenes
- Free Radical Scavengers
- Monoterpenes
- Pyridines
- Reactive Oxygen Species
- 4-cymene
- Osmium
- Glutathione
- Acetylcysteine
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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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