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Asymmetric transfer hydrogenation by synthetic catalysts in cancer cells
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Coverdale, James P. C., Romero-Canelón, Isolda, Sanchez-Cano, Carlos, Clarkson, Guy J., Habtemariam, Abraha, Wills, Martin and Sadler, P. J. (2018) Asymmetric transfer hydrogenation by synthetic catalysts in cancer cells. Nature Chemistry, 10 . pp. 347-354. doi:10.1038/nchem.2918 ISSN 1755-4330.
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Official URL: https://doi.org/10.1038/nchem.2918
Abstract
Catalytic anticancer metallodrugs active at low doses could minimise side-effects, introduce novel mechanisms of action which combat resistance, and widen the spectrum of anticancer drug activity. We have used new highly-stable chiral half-sandwich organometallic Os(II) arene sulfonyl diamine complexes, [Os(arene)(TsDPEN)] to achieve highly enantioselective reduction of pyruvate, a key intermediate in metabolic pathways, both in aqueous model systems and in human cancer cells, using non-toxic concentrations of sodium formate as a hydride source. Importantly the catalytic mechanism generates selectivity towards ovarian cancer cells versus non-cancerous fibroblasts (both ovarian and lung), which are commonly used as models of healthy proliferating cells. The formate precursor N-formylmethionine was explored as an alternative to formate in PC3 prostate cancer cells, which are known to over-express a deformylase enzyme. Transfer hydrogenation catalysts generating reductive stress in cancer cells offer a ground-breaking new approach to cancer therapy.
Item Type: | Journal Article | |||||||||||||||||||||||||||||||||
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Subjects: | R Medicine > RS Pharmacy and materia medica | |||||||||||||||||||||||||||||||||
Divisions: | Faculty of Science, Engineering and Medicine > Science > Chemistry | |||||||||||||||||||||||||||||||||
Library of Congress Subject Headings (LCSH): | Antineoplastic agents, Cancer cells, Hydrogenation, Aromatic compounds | |||||||||||||||||||||||||||||||||
Journal or Publication Title: | Nature Chemistry | |||||||||||||||||||||||||||||||||
Publisher: | Nature Publishing Group | |||||||||||||||||||||||||||||||||
ISSN: | 1755-4330 | |||||||||||||||||||||||||||||||||
Official Date: | 2018 | |||||||||||||||||||||||||||||||||
Dates: |
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Volume: | 10 | |||||||||||||||||||||||||||||||||
Page Range: | pp. 347-354 | |||||||||||||||||||||||||||||||||
DOI: | 10.1038/nchem.2918 | |||||||||||||||||||||||||||||||||
Status: | Peer Reviewed | |||||||||||||||||||||||||||||||||
Publication Status: | Published | |||||||||||||||||||||||||||||||||
Access rights to Published version: | Restricted or Subscription Access | |||||||||||||||||||||||||||||||||
Copyright Holders: | Springer Nature | |||||||||||||||||||||||||||||||||
Date of first compliant deposit: | 10 January 2018 | |||||||||||||||||||||||||||||||||
Date of first compliant Open Access: | 8 July 2018 | |||||||||||||||||||||||||||||||||
RIOXX Funder/Project Grant: |
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