Correlation between cytotoxicity and DNA binding of polypyridyl ruthenium complexes
Language English Country United States Media print
Document type Comparative Study, Journal Article, Research Support, Non-U.S. Gov't
PubMed
7547981
DOI
10.1021/bi00038a034
Knihovny.cz E-resources
- MeSH
- 2,2'-Dipyridyl analogs & derivatives toxicity MeSH
- DNA Adducts * MeSH
- DNA-Directed DNA Polymerase metabolism MeSH
- HeLa Cells MeSH
- Nucleic Acid Conformation MeSH
- Leukemia L1210 MeSH
- Humans MeSH
- Molecular Sequence Data MeSH
- Mice MeSH
- Organometallic Compounds toxicity MeSH
- Antineoplastic Agents pharmacology toxicity MeSH
- Cross-Linking Reagents MeSH
- DNA Replication drug effects MeSH
- Base Sequence MeSH
- DNA, Superhelical drug effects MeSH
- Toxicity Tests MeSH
- Dose-Response Relationship, Drug MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Mice MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Comparative Study MeSH
- Names of Substances
- 2,2'-Dipyridyl MeSH
- DNA Adducts * MeSH
- chloro(2,2'-6',2''-terpyridine)(2,2'-bipyridine)ruthenium MeSH Browser
- dichlorobis(2,2'-bipyridine)ruthenium MeSH Browser
- DNA-Directed DNA Polymerase MeSH
- Organometallic Compounds MeSH
- Antineoplastic Agents MeSH
- Cross-Linking Reagents MeSH
- DNA, Superhelical MeSH
- Tli polymerase MeSH Browser
- trichloro(2,2'-6',2''-terpyridine)ruthenium MeSH Browser
The cytotoxicity of chloropolypyridyl ruthenium complexes of structural formulas [Ru(terpy)-(bpy)Cl]Cl, cis-[Ru(bpy)2Cl2], and mer-[Ru(terpy)Cl3] (terpy = 2,2':6'2"-terpyridine, bpy = 2,2'-bipyridyl) has been studied in murine and human tumor cell lines. The results show that mer-[Ru(terpy)Cl3] exhibits a remarkably higher cytotoxicity than the other complexes. Moreover, investigations of antitumor activity in a standard tumor screen have revealed the highest efficiency for mer-[Ru(terpy)Cl3]. In a cell-free medium, the ruthenium complexes coordinate to DNA preferentially at guanine residues. The resulting adducts can terminate DNA synthesis by thermostable VentR DNA polymerase. The reactivity of the complexes to DNA, their efficiency to unwind closed, negatively supercoiled DNA, and a sequence preference of their DNA adducts (studied by means of replication mapping) do not show a correlation with biological activity. On the other hand, the cytotoxic mer-[Ru(terpy)Cl3] exhibits a significant DNA interstrand cross-linking, in contrast to the inactive complexes which exhibit no such efficacy. The results point to a potential new class of metal-based antitumor compounds acting by a mechanism involving DNA interstrand cross-linking.
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