Metal complexes with 2-acetylpyridine-N(4)-orthochlorophenylthiosemicarbazone: cytotoxicity and effect on the enzymatic activity of thioredoxin reductase and glutathione reductase.

Autor: Parrilha GL; Departamento de Química, Universidade Federal de Minas Gerais, 31270-901, Belo Horizonte, MG, Brazil., Ferraz KS; Departamento de Química, Universidade Federal de Minas Gerais, 31270-901, Belo Horizonte, MG, Brazil., Lessa JA; Departamento de Química Geral e Inorgânica, Instituto de Química, Universidade do Estado do Rio de Janeiro, 20550-013, Rio de Janeiro, RJ, Brazil., de Oliveira KN; Institute of Medicinal and Pharmaceutical Chemistry, Technische Universität Braunschweig, Beethovenstrasse 55, 38106 Braunschweig, Germany., Rodrigues BL; Departamento de Química, Universidade Federal de Minas Gerais, 31270-901, Belo Horizonte, MG, Brazil., Ramos JP; Departamento de Fisiologia e Biofísica, Universidade Federal de Minas Gerais, 31270-901, Belo Horizonte, MG, Brazil., Souza-Fagundes EM; Departamento de Fisiologia e Biofísica, Universidade Federal de Minas Gerais, 31270-901, Belo Horizonte, MG, Brazil., Ott I; Institute of Medicinal and Pharmaceutical Chemistry, Technische Universität Braunschweig, Beethovenstrasse 55, 38106 Braunschweig, Germany., Beraldo H; Departamento de Química, Universidade Federal de Minas Gerais, 31270-901, Belo Horizonte, MG, Brazil. Electronic address: hberaldo@ufmg.br.
Jazyk: angličtina
Zdroj: European journal of medicinal chemistry [Eur J Med Chem] 2014 Sep 12; Vol. 84, pp. 537-44. Date of Electronic Publication: 2014 Jul 17.
DOI: 10.1016/j.ejmech.2014.07.055
Abstrakt: Metal complexes with 2-acetylpyridine-N(4)-orthochlorophenylthiosemicarbazone (H2Ac4oClPh) were assayed for their cytotoxicity against MCF-7 breast adenocarcinoma and HT-29 colon carcinoma cells. The thiosemicarbazone and most of the complexes were highly cytotoxic. H2Ac4oClPh and its gallium(III) and tin(IV) complexes did not show any inhibitory activity against thioredoxin reductase (TrxR) and glutathione reductase (GR). The palladium(II), platinum(II) and bismuth(III) complexes inhibited TrxR at micromolar concentrations but not GR. The antimony(III) and gold(III) complexes strongly inhibited TrxR at submicromolar doses with GR inhibition at higher concentrations. The selectivity of these complexes for TrxR suggests metal binding to a selenol residue in the active site of the enzyme. TrxR inhibition is likely a contributing factor to the mode of action of the gold and antimony derivatives.
(Copyright © 2014 Elsevier Masson SAS. All rights reserved.)
Databáze: MEDLINE
Externí odkaz: