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

作者：Ferraz Karina S O; Da Silva Jeferson G; Costa Flavia M; Mendes Bruno M; Rodrigues Bernardo L; dos Santos Raquel G; Beraldo Heloisa^*

来源：Biometals, 2013, 26(5): 677-691.

DOI：10.1007/s10534-013-9639-x

• Thiosemicarbazones
• Gold(III) complexes
• Platinum(II,IV) complexes
• Cytotoxicity
• Mode of action

Complexes [Au(2Ac4oT)Cl][AuCl2] (1), [Au(H(py)2Ac4mT)Cl-2]Cl center dot H2O (2), [Au(H(py)2Ac4pT)Cl-2]Cl (3), [Pt(H2Ac4oT)Cl]Cl (4), [Pt(2Ac4mT)Cl] center dot 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.

• 出版日期2013-10