Departamento de Química, Universidade Federal de Minas Gerais, Belo Horizonte, MG, 31270-901, Brazil.
Biometals. 2013 Oct;26(5):677-91. doi: 10.1007/s10534-013-9639-x. Epub 2013 Jun 9.
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.
复合物 [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）和[Pt(L)Cl2OH]，L = 2Ac4mT（7）、2Ac4oT（8）、2Ac4pT（9），是用 N(4)-邻位（H2Ac4oT）、N(4)-间位（H2Ac4mT）和 N(4)-对位（H2Ac4pT）甲苯基-2-乙酰基吡啶硫代半卡巴腙与金（III）和铂（II,IV）配位合成的。所有化合物对 U-87 和 T-98 人恶性神经胶质瘤细胞系的细胞毒性活性进行了测定。在 2、5 和 8 中，配位后细胞毒性增强。一般来说，金（III）配合物比铂（II,IV）配合物更具细胞毒性。其中一些化合物的活性比顺铂和金诺芬作为对照物更强。金（III）配合物可能通过抑制硫氧还蛋白还原酶的活性而起作用，而铂（II,IV）配合物的作用模式涉及与 DNA 结合。用研究的化合物处理的细胞呈现出细胞收缩和泡形成等形态变化，这表明细胞通过诱导细胞凋亡而死亡。
