title: N(4)-tolyl-2-acetylpyridine thiosemicarbazones and their platinum(II,IV) and gold(III) complexes: cytotoxicity against human glioma cells and studies on the mode of action.
abstract: Complexes [Au(2Ac4oT)Cl][AuCl2] (1), [Au(Hpy2Ac4mT)Cl2]Cl·H2O (2), [Au(Hpy2Ac4pT)Cl2]Cl (3), [Pt(H2Ac4oT)Cl]Cl (4), [Pt(2Ac4mT)Cl]·H2O (5), [Pt(2Ac4pT)Cl] (6) and [Pt(L)Cl2OH], L = 2Ac4mT (7), 2Ac4oT (8), 2Ac4pT (9) were prepared with N(4)-ortho- (H2Ac4oT), N(4)-meta- (H2Ac4mT) and N(4)-para- (H2Ac4pT) tolyl-2-acetylpyridine thiosemicarbazone. The cytotoxic activities of all compounds were assayed against U-87 and T-98 human malignant glioma cell lines. Upon coordination cytotoxicity improved in 2, 5 and 8. In general, the gold(III) complexes were more cytotoxic than those with platinum(II,IV). Several of these compounds proved to be more active than cisplatin and auranofin used as controls. The gold(III) complexes probably act by inhibiting the activity of thioredoxin reductase enzyme whereas the mode of action of the platinum(II,IV) complexes involves binding to DNA. Cells treated with the studied compounds presented morphological changes such as cell shrinkage and blebs formation, which indicate cell death by apoptosis induction.
authors.affiliation: Departamento de Química, Universidade Federal de Minas Gerais, Belo Horizonte, MG, 31270-901, Brazil.
authors.forename: Karina S O
authors.initials: KS
authors.lastname: Ferraz
authors.forename: Jeferson G
authors.initials: JG
authors.lastname: Da Silva
authors.forename: Flávia M
authors.initials: FM
authors.lastname: Costa
authors.forename: Bruno M
authors.initials: BM
authors.lastname: Mendes
authors.forename: Bernardo L
authors.initials: BL
authors.lastname: Rodrigues
authors.forename: Raquel G
authors.initials: RG
authors.lastname: dos Santos
authors.forename: Heloisa
authors.initials: H
authors.lastname: Beraldo
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D016923:Cell Death / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D005910:Glioma / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D008958:Models, Molecular; D015394:Molecular Structure; D050607:Organogold Compounds / Q000737:chemistry* / Q000494:pharmacology*; D009944:Organoplatinum Compounds / Q000737:chemistry* / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013882:Thiosemicarbazones / Q000737:chemistry* / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D050607:Organogold Compounds; D009944:Organoplatinum Compounds; D013882:Thiosemicarbazones