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Ruthenium polypyridyl complexes and their modes of interaction with DNA : is there a correlation between these interactions and the antitumor activity of the compounds?
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Corral, Eva, Hotze, Anna C. G., den Dulk, Hans, Leczkowska, Anna, Rodger, Alison, Hannon, M. J. (Michael J.) and Reedijk, Jan (2009) Ruthenium polypyridyl complexes and their modes of interaction with DNA : is there a correlation between these interactions and the antitumor activity of the compounds? Journal of Biological Inorganic Chemistry, Vol.14 (No.3). pp. 439-448. doi:10.1007/s00775-008-0460-x ISSN 0949-8257.
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Official URL: http://dx.doi.org/10.1007/s00775-008-0460-x
Abstract
Various interaction modes between a group of six ruthenium polypyridyl complexes and DNA have been studied using a number of spectroscopic techniques. Five mononuclear species were selected with formula [Ru(tpy) L1L2](2-n)?, and one closely related dinuclear cation of formula [{Ru(apy)(tpy)}2{l-H2N(CH2)6NH2}]4?. The ligand tpy is 2,20:60,200-terpyridine and the ligand L1 is a bidentate ligand, namely, apy (2,20-azobispyridine), 2-phenylazopyridine, or 2-phenylpyridinylmethylene amine. The ligand L2 is a labile monodentate ligand, being Cl-, H2O, or CH3CN. All six species containing a labile L2 were found to be able to coordinate to the DNA model base 9-ethylguanine by 1H NMR and mass spectrometry. The dinuclear cationic species, which has no positions available for coordination to a DNA base, was studied for comparison purposes. The interactions between a selection of four representative complexes and calf-thymus DNA were studied by circular and linear dichroism. To explore a possible relation between DNA-binding ability and toxicity, all compounds were screened for anticancer activity in a variety of cancer cell lines, showing in some cases an activity which is comparable to that of cisplatin. Comparison of the details of the compound structures, their DNA binding, and their toxicity allows the exploration of structure–activity relationships that might be used to guide optimization of the activity of agents of this class of compounds.
Item Type: | Journal Article | ||||
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Subjects: | Q Science > QD Chemistry Q Science > QP Physiology |
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Divisions: | Faculty of Science, Engineering and Medicine > Science > Chemistry | ||||
Library of Congress Subject Headings (LCSH): | Ruthenium compounds, DNA-drug interactions, Antineoplastic agents | ||||
Journal or Publication Title: | Journal of Biological Inorganic Chemistry | ||||
Publisher: | Springer | ||||
ISSN: | 0949-8257 | ||||
Official Date: | March 2009 | ||||
Dates: |
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Volume: | Vol.14 | ||||
Number: | No.3 | ||||
Page Range: | pp. 439-448 | ||||
DOI: | 10.1007/s00775-008-0460-x | ||||
Status: | Peer Reviewed | ||||
Access rights to Published version: | Open Access (Creative Commons) | ||||
Date of first compliant deposit: | 16 December 2015 | ||||
Date of first compliant Open Access: | 16 December 2015 | ||||
Funder: | Nederlandse Organisatie voor Wetenschappelijk Onderzoek [Netherlands Organisation for Scientific Research] (NWO), European Union (EU), European Cooperation in the Field of Scientific and Technical Research (Organization) (COST) | ||||
Grant number: | MEIF-CT-2005-024818 (EU), MEST-CT-2005-020842 (EU), D20/0001/00 (COST), D20/0002/00 (COST), D20/0003/01 (COST) |
Data sourced from Thomson Reuters' Web of Knowledge
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