title: Metal complexes with 2-acetylpyridine-N(4)-orthochlorophenylthiosemicarbazone: cytotoxicity and effect on the enzymatic activity of thioredoxin reductase and glutathione reductase.
abstract: 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.
authors: Departamento de Química, Universidade Federal de Minas Gerais, 31270-901, Belo Horizonte, MG, Brazil.
authors: Gabrieli L
authors: GL
authors: Parrilha
authors: Departamento de Química, Universidade Federal de Minas Gerais, 31270-901, Belo Horizonte, MG, Brazil.
authors: Karina S O
authors: KS
authors: Ferraz
authors: Departamento de Química Geral e Inorgânica, Instituto de Química, Universidade do Estado do Rio de Janeiro, 20550-013, Rio de Janeiro, RJ, Brazil.
authors: Josane A
authors: JA
authors: Lessa
authors: Institute of Medicinal and Pharmaceutical Chemistry, Technische Universität Braunschweig, Beethovenstrasse 55, 38106 Braunschweig, Germany.
authors: Kely Navakoski
authors: KN
authors: de Oliveira
authors: Departamento de Química, Universidade Federal de Minas Gerais, 31270-901, Belo Horizonte, MG, Brazil.
authors: Bernardo L
authors: BL
authors: Rodrigues
authors: Departamento de Fisiologia e Biofísica, Universidade Federal de Minas Gerais, 31270-901, Belo Horizonte, MG, Brazil.
authors: Jonas P
authors: JP
authors: Ramos
authors: Departamento de Fisiologia e Biofísica, Universidade Federal de Minas Gerais, 31270-901, Belo Horizonte, MG, Brazil.
authors: Elaine M
authors: EM
authors: Souza-Fagundes
authors: Institute of Medicinal and Pharmaceutical Chemistry, Technische Universität Braunschweig, Beethovenstrasse 55, 38106 Braunschweig, Germany.
authors: Ingo
authors: I
authors: Ott
authors: Departamento de Química, Universidade Federal de Minas Gerais, 31270-901, Belo Horizonte, MG, Brazil. Electronic address: hberaldo@ufmg.br.
authors: Heloisa
authors: H
authors: Beraldo
mesh_terms: D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D002522:Chlorocebus aethiops; D056831:Coordination Complexes / Q000737:chemistry*; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D005980:Glutathione Reductase / Q000037:antagonists & inhibitors*; D019073:HT29 Cells; D006801:Humans; D008099:Liver / Q000201:enzymology; D061986:MCF-7 Cells; D008958:Models, Molecular; D015394:Molecular Structure; D009942:Organometallic Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D013329:Structure-Activity Relationship; D013880:Thioredoxin-Disulfide Reductase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013882:Thiosemicarbazones / Q000737:chemistry*; D014709:Vero Cells
chemical_list: D056831:Coordination Complexes; D004791:Enzyme Inhibitors; D009942:Organometallic Compounds; D013882:Thiosemicarbazones; D005980:Glutathione Reductase; D013880:Thioredoxin-Disulfide Reductase
keywords: Anticancer drugs; Glutathione reductase; Metal complexes; Thioredoxin reductase; Thiosemicarbazones