Departamento de Física e Química da Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Av. do Café s/n, 14040-903 Ribeirão Preto, SP, Brazil.
Escola de Engenharia da Universidade Presbiteriana Mackenzie, Rua da Consolação 930, 01302-907 São Paulo, SP, Brazil.
J Inorg Biochem. 2014 May;134:36-8. doi: 10.1016/j.jinorgbio.2014.01.012. Epub 2014 Jan 24.
In vitro cytotoxicity study of the [Ru3O(CH3COO)6(4-pic)2(NO)]PF6 triruthenium nitrosyl cluster (compound 1, 4-pic=4-methylpyridine) against B16F10 melanoma cell line was evaluated in the presence and absence of visible light irradiation. The nitrosyl cluster 1 showed a significant tumoricidal activity when irradiated at λ=532 nm, reducing cell viability up to 90% at a concentration of 62.5 μM. However, cell death of 60% is also observed in the dark which can be assigned to the NO release mediated by a redox reaction of the cluster in cell medium. This possibility was confirmed by amperometric detection of NO after the addition of ascorbic acid to compound 1 in phosphate buffer. A control experiment was performed with the solvated cluster [Ru3O(CH3COO)6(4-pic)2(CH3OH)]PF6 (compound 2) and no significant lowering of cell viability was observed. These results suggest that the nitrosyl cluster acts as a pro-drug, delivering NO, which is the actual active species.
在体外细胞毒性研究中,研究了[Ru3O(CH3COO)6(4-pic)2(NO)]PF6 三钌亚硝酰基簇(化合物 1,4-pic=4-甲基吡啶)对 B16F10 黑色素瘤细胞系的影响,研究了在可见光照射和不存在可见光照射的情况下的影响。当用 λ=532nm 照射时,亚硝酰基簇 1 表现出显著的杀肿瘤活性,在 62.5μM 的浓度下,将细胞活力降低至 90%。然而,在黑暗中也观察到 60%的细胞死亡,这可以归因于在细胞培养基中通过簇的氧化还原反应介导的 NO 释放。通过在磷酸盐缓冲液中向化合物 1 中添加抗坏血酸后对 NO 进行安培检测,证实了这种可能性。用溶剂化的簇[Ru3O(CH3COO)6(4-pic)2(CH3OH)]PF6(化合物 2)进行了对照实验,没有观察到细胞活力的显著降低。这些结果表明,亚硝酰基簇作为前药起作用,释放出的 NO 是实际的活性物质。