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The potent oxidant anticancer activity of organoiridium catalysts
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Liu, Zhe , Romero-Canelón, Isolda, Qamar, Bushra, Hearn, Jessica M., Habtemariam, Abraha, Barry, Nicolas P. E., Pizarro, Ana M., Clarkson, Guy J. and Sadler, P. J. (2014) The potent oxidant anticancer activity of organoiridium catalysts. Angewandte Chemie International Edition, Volume 53 (Number 15). pp. 3941-3946. doi:10.1002/anie.201311161 ISSN 1433-7851.
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Official URL: http://dx.doi.org/10.1002/anie.201311161
Abstract
Platinum complexes are the most widely used anticancer drugs; however, new generations of agents are needed. The organoiridium(III) complex [(η5-Cpxbiph)Ir(phpy)(Cl)] (1-Cl), which contains π-bonded biphenyltetramethylcyclopentadienyl (Cpxbiph) and C^N-chelated phenylpyridine (phpy) ligands, undergoes rapid hydrolysis of the chlorido ligand. In contrast, the pyridine complex [(η5-Cpxbiph)Ir(phpy)(py)]+ (1-py) aquates slowly, and is more potent (in nanomolar amounts) than both 1-Cl and cisplatin towards a wide range of cancer cells. The pyridine ligand protects 1-py from rapid reaction with intracellular glutathione. The high potency of 1-py correlates with its ability to increase substantially the level of reactive oxygen species (ROS) in cancer cells. The unprecedented ability of these iridium complexes to generate H2O2 by catalytic hydride transfer from the coenzyme NADH to oxygen is demonstrated. Such organoiridium complexes are promising as a new generation of anticancer drugs for effective oxidant therapy.
Item Type: | Journal Article | ||||||||
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Subjects: | Q Science > QD Chemistry Q Science > QH Natural history > QH301 Biology |
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Divisions: | Faculty of Science, Engineering and Medicine > Science > Chemistry Faculty of Science, Engineering and Medicine > Research Centres > Warwick Systems Biology Centre |
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Library of Congress Subject Headings (LCSH): | Antineoplastic agents, Antineoplastic agents -- Development, Iridium compounds, Organoiridium compounds, Organotransition metal compounds | ||||||||
Journal or Publication Title: | Angewandte Chemie International Edition | ||||||||
Publisher: | Wiley - V C H Verlag GmbH & Co. KGaA | ||||||||
ISSN: | 1433-7851 | ||||||||
Official Date: | 7 April 2014 | ||||||||
Dates: |
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Volume: | Volume 53 | ||||||||
Number: | Number 15 | ||||||||
Number of Pages: | 8 | ||||||||
Page Range: | pp. 3941-3946 | ||||||||
DOI: | 10.1002/anie.201311161 | ||||||||
Status: | Peer Reviewed | ||||||||
Publication Status: | Published | ||||||||
Access rights to Published version: | Restricted or Subscription Access | ||||||||
Date of first compliant deposit: | 28 December 2015 | ||||||||
Date of first compliant Open Access: | 28 December 2015 | ||||||||
Funder: | European Research Council (ERC), Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung [Swiss National Science Foundation] (SNSF), University of Warwick. Institute of Advanced Study (IAS), Biotechnology and Biological Sciences Research Council (Great Britain) (BBSRC), Science City Research Alliance, Engineering and Physical Sciences Research Council (EPSRC) | ||||||||
Grant number: | 247450 (ERC), PA00P2_145308 (SNSF), |
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