DNA interactions of monofunctional organometallic ruthenium(II) antitumor complexes in cell-free media
Language English Country United States Media print
Document type Comparative Study, Journal Article, Research Support, Non-U.S. Gov't
PubMed
14516206
DOI
10.1021/bi034933u
Knihovny.cz E-resources
- MeSH
- Benzene Derivatives chemistry metabolism MeSH
- Nucleic Acid Denaturation MeSH
- DNA-Directed RNA Polymerases antagonists & inhibitors genetics metabolism MeSH
- DNA chemistry drug effects metabolism MeSH
- Nucleic Acid Conformation MeSH
- Molecular Sequence Data MeSH
- Organometallic Compounds chemistry metabolism pharmacology MeSH
- Organoplatinum Compounds chemistry pharmacology MeSH
- Plasmids chemistry genetics MeSH
- Polydeoxyribonucleotides chemistry metabolism MeSH
- Antineoplastic Agents chemistry metabolism pharmacology MeSH
- RNA antagonists & inhibitors biosynthesis MeSH
- Ruthenium chemistry metabolism pharmacology MeSH
- Base Sequence MeSH
- Cattle MeSH
- Temperature MeSH
- Viral Proteins MeSH
- Animals MeSH
- Check Tag
- Cattle MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Comparative Study MeSH
- Names of Substances
- bacteriophage T7 RNA polymerase MeSH Browser
- Benzene Derivatives MeSH
- calf thymus DNA MeSH Browser
- DNA-Directed RNA Polymerases MeSH
- DNA MeSH
- Organometallic Compounds MeSH
- Organoplatinum Compounds MeSH
- Polydeoxyribonucleotides MeSH
- Antineoplastic Agents MeSH
- RNA polymerase SP6 MeSH Browser
- RNA MeSH
- Ruthenium MeSH
- Viral Proteins MeSH
Modifications of natural DNA in a cell-free medium by antitumor monodentate Ru(II) arene compounds of the general formula [(eta(6)-arene)Ru(en)Cl](+) (arene = biphenyl, dihydroanthracene, tetrahydroanthracene, p-cymene, or benzene; en = ethylenediamine) were studied by atomic absorption, melting behavior, transcription mapping, circular and linear dichroism, plasmid unwinding, competitive ethidium displacement, and differential pulse polarography. The results indicate that these complexes bind preferentially to guanine residues in double-helical DNA. The data are consistent with DNA binding of the complexes containing biphenyl, dihydroanthracene, or tetrahydroanthracene ligands that involves combined coordination to G N7 and noncovalent, hydrophobic interactions between the arene ligand and DNA, which may include arene intercalation and minor groove binding. In contrast, the single hydrocarbon rings in the p-cymene and benzene ruthenium complexes cannot interact with double-helical DNA by intercalation. Interestingly, the adducts of the complex containing p-cymene ligand, which has methyl and isopropyl substituents, distort the conformation and thermally destabilize double-helical DNA distinctly more than the adducts of the three multiring ruthenium arene compounds. It has been suggested that the different character of conformational alterations induced in DNA, and the resulting thermal destabilization, may affect differently further "downstream" effects of damaged DNA and consequently may result in different biological effects of this new class of metal-based antitumor compounds. The results point to a unique profile of DNA binding for Ru(II) arene compounds, suggesting that a search for new anticancer compounds based on this class of complexes may also lead to an altered profile of biological activity in comparison with that of metal-based antitumor drugs already used in the clinic or currently on clinical trials.
References provided by Crossref.org
Biophysical studies on the stability of DNA intrastrand cross-links of transplatin
