title: Gold(I) complexes with thiosemicarbazones: cytotoxicity against human tumor cell lines and inhibition of thioredoxin reductase activity.
abstract: Complexes [Au(H2Ac4DH)Cl]∙MeOH (1) [Au(H(2)2Ac4Me)Cl]Cl (2) [Au(H(2)2Ac4Ph)Cl]Cl∙2H(2)O (3) and [Au(H(2)2Bz4Ph)Cl]Cl (4) were obtained with 2-acetylpyridine thiosemicarbazone (H2Ac4DH), its N(4)-methyl (H2Ac4Me) and N(4)-phenyl (H2Ac4Ph) derivatives, as well as with N(4)-phenyl 2-benzoylpyridine thiosemicarbazone (H2Bz4Ph). The compounds were cytotoxic to Jurkat (immortalized line of T lymphocyte), HL-60 (acute myeloid leukemia), MCF-7 (human breast adenocarcinoma) and HCT-116 (colorectal carcinoma) tumor cell lines. Jurkat and HL-60 cells were more sensitive than MCF-7 and HCT-116 cells. Upon coordinating to the gold(I) metal centers in complexes (2) and (4), the cytotoxic activity of the H2Ac4Me and H2Bz4Ph ligands increased against the HL-60 and Jurkat tumor cell lines. 2 was more active than auranofin against both leukemia cells. Most of the studied compounds were less toxic than auranofin to peripheral blood mononuclear cells (PBMC). All compounds induced DNA fragmentation in HL-60 and Jurkat cells indicating their pro-apoptotic potential. Complex (2) strongly inhibited the activity of thioredoxin reductase (TrxR), which suggests inhibition of TrxR to be part of its mechanism of action.
authors: Departamento de Química, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil.
authors: Josane A
authors: JA
authors: Lessa
authors: Juliana C
authors: JC
authors: Guerra
authors: Luana F
authors: LF
authors: de Miranda
authors: Carla F D
authors: CF
authors: Romeiro
authors: Jeferson G
authors: JG
authors: Da Silva
authors: Isolda C
authors: IC
authors: Mendes
authors: Nivaldo L
authors: NL
authors: Speziali
authors: Elaine M
authors: EM
authors: Souza-Fagundes
authors: Heloisa
authors: H
authors: Beraldo
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D001310:Auranofin / Q000494:pharmacology; D045744:Cell Line, Tumor; D002470:Cell Survival; D056831:Coordination Complexes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D018360:Crystallography, X-Ray; D053938:DNA Fragmentation; D004278:DNA, Superhelical / Q000737:chemistry; D006046:Gold; D006801:Humans; D020128:Inhibitory Concentration 50; D007963:Leukocytes, Mononuclear / Q000187:drug effects; D008958:Models, Molecular; D008968:Molecular Conformation; D013880:Thioredoxin-Disulfide Reductase / Q000037:antagonists & inhibitors*; D013882:Thiosemicarbazones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D056831:Coordination Complexes; D004278:DNA, Superhelical; D013882:Thiosemicarbazones; D001310:Auranofin; C033836:2-acetylpyridine thiosemicarbazone; D006046:Gold; D013880:Thioredoxin-Disulfide Reductase