Organometallic Osmium Arene Complexes with Potent Cancer Cell Cytotoxicity
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 can...
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| Published in | Journal of medicinal chemistry Vol. 53; no. 22; pp. 8192 - 8196 |
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| Main Authors | , , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
United States
American Chemical Society
25.11.2010
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| Abstract | 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. |
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| AbstractList | 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. 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.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. 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. |
| Author | Fu, Ying Shnyder, Steven D Habtemariam, Abraha van Rijt, Sabine H Healey, David J Pizarro, Ana M Cooper, Patricia A Clarkson, Guy J Sadler, Peter J |
| Author_xml | – sequence: 1 givenname: Ying surname: Fu fullname: Fu, Ying – sequence: 2 givenname: Abraha surname: Habtemariam fullname: Habtemariam, Abraha – sequence: 3 givenname: Ana M surname: Pizarro fullname: Pizarro, Ana M – sequence: 4 givenname: Sabine H surname: van Rijt fullname: van Rijt, Sabine H – sequence: 5 givenname: David J surname: Healey fullname: Healey, David J – sequence: 6 givenname: Patricia A surname: Cooper fullname: Cooper, Patricia A – sequence: 7 givenname: Steven D surname: Shnyder fullname: Shnyder, Steven D – sequence: 8 givenname: Guy J surname: Clarkson fullname: Clarkson, Guy J – sequence: 9 givenname: Peter J surname: Sadler fullname: Sadler, Peter J email: P.J.Sadler@warwick.ac.uk |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/20977192$$D View this record in MEDLINE/PubMed |
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| Snippet | Iodido osmium(II) complexes [Os(η6-arene)(XY)I]+ (XY = p-hydroxy or p-dimethylaminophenylazopyridine, arene = p-cymene or biphenyl) are potently cytotoxic at... Iodido osmium(II) complexes [Os(η(6)-arene)(XY)I](+) (XY = p-hydroxy or p-dimethylaminophenylazopyridine, arene = p-cymene or biphenyl) are potently cytotoxic... |
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| SubjectTerms | 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 |
| Title | Organometallic Osmium Arene Complexes with Potent Cancer Cell Cytotoxicity |
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