(Aminoethanol)dichloroplatinum(II) complexes: Influence of the hydroxyethyl moiety on 5'-GMP and DNA binding, intramolecular stability, the partition coefficient and anticancer activity
- Author(s)
- Marc S. Robillard, Mathea Sophia Galanski, Wolfgang Zimmermann, Bernhard Keppler, Jan Reedijk
- Abstract
The influence of tethered hydroxyl groups on the binding behavior of the three (aminoethanol)dichloroplatinum complexes, dichloro(N,N'-bis(2-hydroxyethyl)ethylenediamine)-platinum(II) (1), dichloro(N-(2-hydroxyethyl)ethylenediamine)platinum(II) (2) and cis-dichlorobis(2-hydroxyethylamine)platinum(II) (3) towards 5'-GMP and DNA was investigated by 1H NMR and rb measurements, respectively. At pH 7.2, the sequence of reactivity with 5'-GMP is 1>2Ÿ3. Complex 3 reacts very slowly with 5'-GMP and DNA and the amount and lifetime of the intermediate 5'-GMP monoadduct are much larger than for 1 and 2. At pH 5.5, the reaction of 3 with 5'-GMP is markedly accelerated and very small amounts of monoadduct are observed, indicating a pH-dependent ability of the pendant hydroxyl group to interact with the platinum moiety. In addition, the effect of the hydroxyethyl functionality on octanol/water partitioning and in vitro anticancer activity was studied. No correlation between lipophilicity and anticancer activity was detected. Furthermore, the lipophilicity and anticancer activity could not be directly correlated to 5'-GMP or DNA binding activity. Copyright Œ 2002 .
- Organisation(s)
- Department of Inorganic Chemistry
- External organisation(s)
- Leiden University, University of Vienna
- Journal
- Journal of Inorganic Biochemistry
- Volume
- 88
- Pages
- 254-259
- No. of pages
- 6
- ISSN
- 0162-0134
- DOI
- https://doi.org/10.1016/S0162-0134(01)00362-2
- Publication date
- 2002
- Peer reviewed
- Yes
- Austrian Fields of Science 2012
- 1040 Chemistry
- Portal url
- https://ucrisportal.univie.ac.at/en/publications/f406ffbd-1111-46ba-84a0-f61454ff23d3