Gallium(III) and iron(III) complexes of alpha-N-heterocyclic thiosemicarbazones: Synthesis, characterization, cytotoxicity, and interaction with ribonucleotide reductase

Author(s)
Christian Kowol, Roland Berger, Rene Eichinger, Alexander Roller, Michael Jakupec, Peter P. Schmidt, Vladimir Arion, Bernhard Keppler
Abstract

A series of gallium(III) and iron(III) complexes with five different 4N-substituted ?-N-heterocyclic thiosemicarbazones, viz., 2-acetylpyridine N,N-dimethylthiosemicarbazone (1), 2-acetylpyridine N-pyrrolidinylthiosemicarbazone (2), acetylpyrazine N,N- dimethylthiosemicarbazone (3), acetylpyrazine N-pyrrolidinylthiosemicarbazone (4), and acetylpyrazine N-piperidinylthiosemicarbazone (5), with the general formula [GaLCl2] (HL = 1 and 2) and [ML2][Y] (M = Ga, HL = 1-5, Y = PF6; M = Fe, HL = 1-5, Y = FeCl4 and PF 6) were synthesized and characterized by elemental analysis, a number of spectroscopic methods (NMR, IR, UV-vis), mass spectrometry, and X-ray crystallography. The in vitro antitumor potency was studied in two human cancer cell lines (41M and SK-BR-3). The central metal ions exert pronounced effects in a divergent manner: gallium(III) enhances, whereas iron(III) weakens the cytotoxicity of the ligands. The capacity of ligand 1 and its Ga(III) and Fe(III) complexes to destroy the tyrosyl radical of the presumed target ribonucleotide reductase is reported. © 2007 American Chemical Society.

Organisation(s)
Department of Inorganic Chemistry
External organisation(s)
Max-Planck-Institut für bioanorganische Chemie
Journal
Journal of Medicinal Chemistry
Volume
50
Pages
1254-1265
No. of pages
12
ISSN
0022-2623
Publication date
2007
Peer reviewed
Yes
Austrian Fields of Science 2012
104003 Inorganic chemistry
Sustainable Development Goals
SDG 3 - Good Health and Well-being
Portal url
https://ucrisportal.univie.ac.at/en/publications/af592a60-6860-4c74-bee9-d2195ef9525d