期刊
JOURNAL OF ORGANOMETALLIC CHEMISTRY
卷 851, 期 -, 页码 68-78出版社
ELSEVIER SCIENCE SA
DOI: 10.1016/j.jorganchem.2017.09.005
关键词
Palladacycles; Metallacycles; DNA binding studies; Anti-cancer agents; Metallodrugs; 1,3,5-Triaza-7-phosphaadamantane complexes
资金
- Medical Research council of South Africa
- National Research Foundation of South Africa
- Research committee of Stellenbosch University
- Research committee of University of Cape Town
A series of novel mononuclear 1,3,5-triaza-7-phosphaadamantane (PTA)-based palladacycles were prepared by cleaving m-Cl binuclear orthopalladated dimers of substituted benzylidene-2,6-diisopropylphenylamines. All complexes were fully characterized using IR and NMR spectroscopy, mass spectrometry as well as elemental analysis. In-vitro evaluation of the complexes as anti-cancer agents against the breast-cancer cell lines MCF7 and MDA-MB 231 as well the melanoma cell line ME1402 shows that four of the five complexes tested are active. These palladacycles exhibit their cytotoxicity by inducing DNA damage which subsequently triggers apoptosis. DNA binding studies using electrophoresis and spectroscopic techniques, such as UV-Vis and circular dichroism spectroscopy, confirms that the palladacycle, C2 definitely interacts with DNA. Results from these DNA binding experiments seem to rule out co-valent and intercalative binding, pointing rather to a non-covalent interaction, with electrostatic binding being the most likely possibility. It is envisioned that this would probably involve a hydrolysed or solvated derivative of C2. (C) 2017 Elsevier B.V. All rights reserved.
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