Impact of metal coordination on cytotoxicity of 3-aminopyridine-2- carboxaldehyde thiosemicarbazone (Triapine) and novel insights into terminal dimethylation
- Author(s)
- Christian Kowol, Robert Trondl, Petra Heffeter, Vladimir Arion, Michael Jakupec, Alexander Roller, Mathea Sophia Galanski, Walter Berger, Bernhard Keppler
- Abstract
The first metal complexes of 3-aminopyridine-2-carboxaldehyde thiosemicarbazone (Triapine) were synthesized. Triapine was prepared by a novel three-step procedure in 64% overall yield. In addition, a series of related ligands, namely, 2-formylpyridine thiosemicarbazone, 2-acetylpyridine thiosemicarbazone, 2-pyridineformamide thiosemicarbazone, and their N 4-dimethylated derivatives (including the N4-dimethylated analogue of Triapine) were prepared, along with their corresponding gallium(III) and iron(III) complexes with the general formula [M(L)2] +, where HL is the respective thiosemicarbazone. The compounds were characterized by elemental analysis, 1H and 13C NMR, IR and UV-vis spectroscopies, mass spectrometry, and cyclic voltammetry. In addition, Triapine and its iron(III) and gallium(III) complexes were studied by X-ray crystallography. All ligands and complexes were tested for their in vitro antiproliferative activity in two human cancer cell lines (41M and SK-BR-3), and structure-activity relationships were established. In general, the coordination to gallium(III) increased the cytotoxicity while the iron(III) complexes show reduced cytotoxic activity compared to the metal-free thiosemicarbazones. Selected compounds were investigated for the capacity of inhibiting ribonucleotide reductase by incorporation of 3H-cytidine into DNA.
- Organisation(s)
- Department of Inorganic Chemistry
- External organisation(s)
- Medizinische Universität Wien
- Journal
- Journal of Medicinal Chemistry
- Volume
- 52
- Pages
- 5032-5043
- No. of pages
- 12
- ISSN
- 0022-2623
- DOI
- https://doi.org/10.1021/jm900528d
- Publication date
- 2009
- Peer reviewed
- Yes
- Austrian Fields of Science 2012
- 104003 Inorganic chemistry, 104002 Analytical chemistry, 301114 Cell biology
- Sustainable Development Goals
- SDG 3 - Good Health and Well-being
- Portal url
- https://ucrisportal.univie.ac.at/en/publications/2f5ac294-d3f4-44d0-b842-a2bc2f0c32ac