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The contrasting activity of iodido versus chlorido ruthenium and osmium arene azo- and imino-pyridine anticancer complexes : control of cell selectivity, cross-resistance, p53 dependence, and apoptosis pathway
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Romero-Canelón, Isolda, Salassa, Luca and Sadler, P. J. (2013) The contrasting activity of iodido versus chlorido ruthenium and osmium arene azo- and imino-pyridine anticancer complexes : control of cell selectivity, cross-resistance, p53 dependence, and apoptosis pathway. Journal of Medicinal Chemistry, Volume 56 (Number 3). pp. 1291-1300. doi:10.1021/jm3017442 ISSN 0022-2623.
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Official URL: http://dx.doi.org/10.1021/jm3017442
Abstract
Organometallic half-sandwich complexes [M(p-cymene)(azo/imino-pyridine)X]+ where M = RuII or OsII and X ═ Cl or I, exhibit potent antiproliferative activity toward a range of cancer cells. Not only are the iodido complexes more potent than the chlorido analogues, but they are not cross-resistant with the clinical platinum drugs cisplatin and oxaliplatin. They are also more selective for cancer cells versus normal cells (fibroblasts) and show high accumulation in cell membranes. They arrest cell growth in G1 phase in contrast to cisplatin (S phase) with a high incidence of late-stage apoptosis. The iodido complexes retain potency in p53 mutant colon cells. All complexes activate caspase 3. In general, antiproliferative activity is greatly enhanced by low levels of the glutathione synthase inhibitor l-buthionine sulfoxime. The work illustrates how subtle changes to the design of low-spin d6 metal complexes can lead to major changes in cellular metabolism and to potent complexes with novel mechanisms of anticancer activity.
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): | Cancer -- Treatment, Cytochemistry, Cell metabolism, Biochemistry | ||||
Journal or Publication Title: | Journal of Medicinal Chemistry | ||||
Publisher: | American Chemical Society | ||||
ISSN: | 0022-2623 | ||||
Official Date: | 2013 | ||||
Dates: |
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Volume: | Volume 56 | ||||
Number: | Number 3 | ||||
Page Range: | pp. 1291-1300 | ||||
DOI: | 10.1021/jm3017442 | ||||
Status: | Peer Reviewed | ||||
Publication Status: | Published | ||||
Access rights to Published version: | Open Access (Creative Commons) | ||||
Date of first compliant deposit: | 24 December 2015 | ||||
Date of first compliant Open Access: | 24 December 2015 |
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