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DNA interactions of monofunctional organometallic osmium(II) antitumor complexes in cell-free media
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Kostrhunova, Hana, Florian, Jakub, Novakova, Olga, Peacock, Anna F. A., Sadler, P. J. and Brabec, V. (Viktor). (2008) DNA interactions of monofunctional organometallic osmium(II) antitumor complexes in cell-free media. Journal of Medicinal Chemistry, Vol.51 (No.12). pp. 3635-3643. ISSN 0022-2623
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Official URL: http://dx.doi.org/10.1021/jm701538w
Abstract
This work is the first in-depth study of osmium binding to DNA and confirms the pharmacological activity of a new class of anticancer metallodrugs. We investigated the interactions between the potential biological target DNA and four osmium(II) arene complexes, of the type [(eta(6)-arene)Os(LL)Cl](n+), where arene = biphenyl or p-cymene and LL = ethylenediamine, picolinate, or oxinate in an effort to understand their mechanism of action. Most notably. we show that these complexes bind to DNA. DNA adducts of the Os-II complexes that exhibit promising cytotoxic effects in ovarian tumor cell lines largely distort its conformation. The data are consistent with DNA binding of the complexes containing biphenyl as the arene ligand that involves combined coordination to guanine residues and noncovalent interactions between the arene ligand and DNA. The results also indicate both a mechanism of action and a detoxification mechanism for Os-II arene compounds different from those of cisplatin.
| Item Type: | Journal Article |
|---|---|
| Subjects: | Q Science > QD Chemistry R Medicine > RM Therapeutics. Pharmacology |
| Divisions: | Faculty of Science > Chemistry |
| Library of Congress Subject Headings (LCSH): | Osmium, DNA, Organometallic compounds, Antineoplastic agents -- Development, Transition metal complexes |
| Journal or Publication Title: | Journal of Medicinal Chemistry |
| Publisher: | American Chemical Society |
| ISSN: | 0022-2623 |
| Official Date: | 26 June 2008 |
| Volume: | Vol.51 |
| Number: | No.12 |
| Number of Pages: | 9 |
| Page Range: | pp. 3635-3643 |
| Identification Number: | 10.1021/jm701538w |
| Status: | Peer Reviewed |
| Publication Status: | Published |
| Access rights to Published version: | Restricted or Subscription Access |
| Funder: | Czech Republic. Ministerstvo školství, mládeže a tělovýchovy [Czech Republic. Ministry of Education, Youth, and Sport], Akademie věd České republiky [Academy of Sciences of the Czech Republic] (ASCR), Ministerstvo zdravotnictví České republiky [Ministry of Health of the Czech Republic] (MZCR), Engineering and Physical Sciences Research Council (EPSRC), Wellcome Trust (London, England) |
| Grant number: | MSMT LC06030 (CRMEYS), 6198959216 (CRMEYS), ME08017 (CRMEYS), OC08003 (CRMEYS), 1QS500040581 (ASCR), KAN200200651 (ASCR), AV0Z50040507 (ASCR), AV0Z50040702 (ASCR), IAA400040803 (ASCR), NR8562-4/2005 (MZCR) |
| URI: | http://wrap.warwick.ac.uk/id/eprint/29835 |
Data sourced from Thomson Reuters' Web of Knowledge
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