DNA interactions of monofunctional organometallic osmium(II) antitumor complexes in cell-free media
Language English Country United States Media print
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
18494458
DOI
10.1021/jm701538w
Knihovny.cz E-resources
- MeSH
- DNA Adducts chemistry MeSH
- Cell-Free System MeSH
- Drug Resistance, Neoplasm MeSH
- Cisplatin chemistry MeSH
- DNA chemistry metabolism MeSH
- Ethidium MeSH
- Fluorescent Dyes MeSH
- Spectrometry, Fluorescence MeSH
- Intercalating Agents MeSH
- Humans MeSH
- Molecular Conformation MeSH
- Cell Line, Tumor MeSH
- Oligonucleotides chemistry MeSH
- Organometallic Compounds chemistry metabolism MeSH
- Osmium * MeSH
- Antineoplastic Agents chemistry metabolism MeSH
- Drug Screening Assays, Antitumor MeSH
- DNA, Superhelical chemistry MeSH
- Transition Temperature MeSH
- Structure-Activity Relationship MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- DNA Adducts MeSH
- calf thymus DNA MeSH Browser
- Cisplatin MeSH
- DNA MeSH
- Ethidium MeSH
- Fluorescent Dyes MeSH
- Intercalating Agents MeSH
- Oligonucleotides MeSH
- Organometallic Compounds MeSH
- Osmium * MeSH
- Antineoplastic Agents MeSH
- DNA, Superhelical MeSH
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 OsII 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 OsII arene compounds different from those of cisplatin.
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