Gallium(III) and Iron(III) Complexes of -N-Heterocyclic Thiosemicarbazones: Synthesis, Characterization, Cytotoxicity, and Interacti
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- 作者：Christian R. Kowol ; Roland Berger ; Rene Eichinger ; Alexander Roller ; Michael A. Jakupec ; Peter P. Schmidt ; Vladimir B. Arion ; Bernhard K. Keppler
- 刊名：Journal of Medicinal Chemistry
- 出版年：2007
- 出版时间：March 22, 2007
- 年：2007
- 卷：50
- 期：6
- 页码：1254 - 1265
- 全文大小：628K
- 年卷期：v.50,no.6(March 22, 2007)
- ISSN：1520-4804
文摘
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 PF6)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 intwo human cancer cell lines (41M and SK-BR-3). The central metal ions exert pronounced effects in adivergent manner: gallium(III) enhances, whereas iron(III) weakens the cytotoxicity of the ligands. Thecapacity of ligand 1 and its Ga(III) and Fe(III) complexes to destroy the tyrosyl radical of the presumedtarget ribonucleotide reductase is reported.
-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 PF6)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 intwo human cancer cell lines (41M and SK-BR-3). The central metal ions exert pronounced effects in adivergent manner: gallium(III) enhances, whereas iron(III) weakens the cytotoxicity of the ligands. Thecapacity of ligand 1 and its Ga(III) and Fe(III) complexes to destroy the tyrosyl radical of the presumedtarget ribonucleotide reductase is reported.