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Transfer hydrogenation catalysis in cells as a new approach to anticancer drug design
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Soldevila-Barreda, Joan J., Romero-Canelón, Isolda, Habtemariam, Abraha and Sadler, P. J. (2015) Transfer hydrogenation catalysis in cells as a new approach to anticancer drug design. Nature Communications, 6 . pp. 1-9. 6582. doi:10.1038/ncomms7582 ISSN 2041-1723.
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Official URL: http://dx.doi.org/10.1038/ncomms7582
Abstract
Organometallic complexes are effective hydrogenation catalysts for organic reactions. For example, Noyori-type ruthenium complexes catalyse reduction of ketones by transfer of hydride from formate. Here we show that such catalytic reactions can be achieved in cancer cells, offering a new strategy for the design of safe metal-based anticancer drugs. The activity of ruthenium(II) sulfonamido ethyleneamine complexes towards human ovarian cancer cells is enhanced by up to 50 × in the presence of low non-toxic doses of formate. The extent of conversion of coenzyme NAD+ to NADH in cells is dependent on formate concentration. This novel reductive stress mechanism of cell death does not involve apoptosis or perturbation of mitochondrial membrane potentials. In contrast, iridium cyclopentadienyl catalysts cause cancer cell death by oxidative stress. Organometallic complexes therefore have an extraordinary ability to modulate the redox status of cancer cells.
Item Type: | Journal Article | ||||||||
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Subjects: | Q Science > QD Chemistry | ||||||||
Divisions: | Faculty of Science, Engineering and Medicine > Science > Chemistry | ||||||||
Library of Congress Subject Headings (LCSH): | Organometallic compounds, Hydrogenation, Antineoplastic agents | ||||||||
Journal or Publication Title: | Nature Communications | ||||||||
Publisher: | Nature Publishing Group | ||||||||
ISSN: | 2041-1723 | ||||||||
Official Date: | 20 March 2015 | ||||||||
Dates: |
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Volume: | 6 | ||||||||
Number of Pages: | 9 | ||||||||
Page Range: | pp. 1-9 | ||||||||
Article Number: | 6582 | ||||||||
DOI: | 10.1038/ncomms7582 | ||||||||
Status: | Peer Reviewed | ||||||||
Publication Status: | Published | ||||||||
Access rights to Published version: | Open Access (Creative Commons) | ||||||||
Date of first compliant deposit: | 30 December 2015 | ||||||||
Date of first compliant Open Access: | 30 December 2015 | ||||||||
Funder: | European Research Council (ERC), Engineering and Physical Sciences Research Council (EPSRC), University of Warwick. Institute of Advanced Study (IAS), Birmingham Science City, European Regional Development Fund (ERDF), Advantage West Midlands (AWM) | ||||||||
Grant number: | 247450 (ERC), EP/F034210/1 (EPSRC) |
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