Structural characterization, DNA interactions, and cytotoxicity of new transplatin analogues containing one aliphatic and one planar heterocyclic amine ligand
Language English Country United States Media print
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
16610807
DOI
10.1021/jm0602514
Knihovny.cz E-resources
- MeSH
- Amines chemistry MeSH
- Circular Dichroism MeSH
- Cisplatin chemical synthesis chemistry pharmacology MeSH
- DNA chemistry drug effects MeSH
- Heterocyclic Compounds, 1-Ring chemical synthesis chemistry pharmacology MeSH
- Crystallography, X-Ray MeSH
- Humans MeSH
- Ligands MeSH
- Models, Molecular MeSH
- Molecular Sequence Data MeSH
- Molecular Structure MeSH
- Cell Line, Tumor MeSH
- Cell Proliferation drug effects MeSH
- Drug Screening Assays, Antitumor MeSH
- Base Sequence MeSH
- Thiourea chemistry MeSH
- Binding Sites 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
- Amines MeSH
- Cisplatin MeSH
- DNA MeSH
- Heterocyclic Compounds, 1-Ring MeSH
- Ligands MeSH
- Thiourea MeSH
- transplatin MeSH Browser
We report in the present work new analogues of clinically ineffective transplatin in which one ammine group was replaced by aliphatic and the other by a planar heterocyclic ligand, namely trans-[PtCl(2)(isopropylamine)(3-(hydroxymethyl)-pyridine)], 1, and trans-[PtCl(2)(isopropylamine)(4-(hydroxymethyl)-pyridine)], 2. The new compounds, in comparison with parent transplatin, exhibit radically enhanced activity in tumor cell lines both sensitive and in particular resistant to cisplatin. Concomitantly, the DNA binding mode of 1 and 2 compared to parent transplatin and other antitumor analogues of transplatin in which only one ammine group was replaced is also different. The results also suggest that the reactions of glutathione and metallothionein-2 with compounds 1 and 2 do not play a crucial role in their overall biological effects. In addition, the monofunctional adducts of 1 and 2 are quenched by glutathione considerably less than the adducts of transplatin, which may potentiate cytotoxic effects of these new platinum complexes.
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