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Correlation between cytotoxicity and DNA binding of polypyridyl ruthenium complexes
O Novakova, J Kasparkova, O Vrana, Vliet PM van, J Reedijk, V Brabec
Jazyk angličtina Země Spojené státy americké
Typ dokumentu srovnávací studie, práce podpořená grantem
Grantová podpora
IZ1893
MZ0
CEP - Centrální evidence projektů
PubMed
7547981
DOI
10.1021/bi00038a034
Knihovny.cz E-zdroje
- MeSH
- 2,2'-dipyridyl * analogy a deriváty toxicita MeSH
- adukty DNA * MeSH
- DNA-dependentní DNA-polymerasy metabolismus MeSH
- HeLa buňky MeSH
- konformace nukleové kyseliny MeSH
- leukemie L1210 MeSH
- lidé MeSH
- molekulární sekvence - údaje MeSH
- myši MeSH
- organokovové sloučeniny * toxicita MeSH
- protinádorové látky farmakologie toxicita MeSH
- reagencia zkříženě vázaná MeSH
- replikace DNA účinky léků MeSH
- sekvence nukleotidů MeSH
- superhelikální DNA účinky léků MeSH
- testy toxicity MeSH
- vztah mezi dávkou a účinkem léčiva MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- práce podpořená grantem MeSH
- srovnávací studie MeSH
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.
Citace poskytuje Crossref.org
Literatura
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