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The contrasting catalytic efficiency and cancer cell antiproliferative activity of stereoselective organoruthenium transfer hydrogenation catalysts
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Fu, Ying, Sanchez-Cano, Carlos, Soni, Rina, Romero-Canelón, Isolda, Hearn, Jessica M., Liu, Zhe, Wills, Martin and Sadler, P. J. (2016) The contrasting catalytic efficiency and cancer cell antiproliferative activity of stereoselective organoruthenium transfer hydrogenation catalysts. Dalton Transactions, 45 (20). pp. 8367-8378. doi:10.1039/c6dt01242f ISSN 1477-9226.
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Official URL: http://dx.doi.org/10.1039/C6DT01242F
Abstract
The rapidly growing area of catalytic ruthenium chemistry has provided new complexes with potential as organometallic anticancer agents with novel mechanisms of action. Here we report the anticancer activity of four neutral organometallic RuII arene N-tosyl-1,2-diphenylethane-1,2-diamine (TsDPEN) tethered transfer hydrogenation catalysts. The enantiomers (R,R)-[Ru(η6-C6H5(CH2)3-TsDPEN-N-Me)Cl] (8) and (S,S)-[Ru(η6-C6H5(CH2)3-TsDPEN-N-Me)Cl] (8a) exhibited higher potency than cisplatin against A2780 human ovarian cancer cells. When the N-methyl was replaced by N–H, i.e. to give (R,R)-[Ru(η6-Ph(CH2)3-TsDPEN-NH)Cl] (7) and (S,S)-[Ru(η6-Ph(CH2)3-TsDPEN-NH)Cl] (7a), respectively, anticancer activity decreased >5-fold. Their antiproliferative activity appears to be linked to their ability to accumulate in cells, and their mechanism of action might involve inhibition of tubulin polymerisation. This appears to be the first report of the potent anticancer activity of tethered RuII arene complexes, and the structure–activity relationship suggests that the N-methyl substituents are important for potency. In the National Cancer Institute 60-cancer-cell-line screen, complexes 8 and 8a exhibited higher activity than cisplatin towards a broad range of cancer cell lines. Intriguingly, in contrast to their potent anticancer properties, complexes 8/8a are poor catalysts for asymmetric transfer hydrogenation, whereas complexes 7/7a are effective asymmetric hydrogenation catalysts.
| Item Type: | Journal Article | ||||||||||
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| Subjects: | Q Science > QD Chemistry R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer) |
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| Divisions: | Faculty of Science, Engineering and Medicine > Science > Chemistry | ||||||||||
| Library of Congress Subject Headings (LCSH): | Antineoplastic agents, Tubulins, Cisplatin, Organometallic chemistry | ||||||||||
| Journal or Publication Title: | Dalton Transactions | ||||||||||
| Publisher: | Royal Society of Chemistry | ||||||||||
| ISSN: | 1477-9226 | ||||||||||
| Official Date: | 28 May 2016 | ||||||||||
| Dates: |
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| Volume: | 45 | ||||||||||
| Number: | 20 | ||||||||||
| Page Range: | pp. 8367-8378 | ||||||||||
| DOI: | 10.1039/c6dt01242f | ||||||||||
| Status: | Peer Reviewed | ||||||||||
| Publication Status: | Published | ||||||||||
| Access rights to Published version: | Open Access (Creative Commons) | ||||||||||
| Date of first compliant deposit: | 11 July 2016 | ||||||||||
| Date of first compliant Open Access: | 11 July 2016 | ||||||||||
| Funder: | European Research Council (ERC), Engineering and Physical Sciences Research Council (EPSRC), Birmingham Science City, European Regional Development Fund (ERDF), Advantage West Midlands (AWM), University of Warwick Postgraduate Research Scholarship | ||||||||||
| Grant number: | 7450 BIOINCMED (ERC), EP/F034210/1 |
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