Departamento de Física e Química, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Av. Prof. Zeferino Vaz s/n, CEP, 14040-903, Ribeirão Preto, SP, Brazil; Departamento de Química Geral e Inorgânica, Instituto de Química, Universidade Federal da Bahia, Rua Barão de Geremoabo, 147, Campus Universitário de Ondina, C.E.P. 40.170-115, Salvador, BA, Brazil.
Departamento de Física e Química, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Av. Prof. Zeferino Vaz s/n, CEP, 14040-903, Ribeirão Preto, SP, Brazil.
Nitric Oxide. 2019 May 1;86:38-47. doi: 10.1016/j.niox.2019.02.005. Epub 2019 Feb 19.
This work investigates how the luminescent ruthenium-nitrite complexes cis-Ru(py-bodipy)(dcbpy)(NO) (I) and cis-Ru(py-bodipy)(dcbpy-aminopropyl-β-lactose)(NO) (II) behave toward the melanoma cancer cell line B16F10. The chemical structure and purity of the synthesized complexes were analyzed by UV-Visible and FTIR spectroscopy, MALDI, HPLC, and H NMR. Spectrofluorescence helped to determine the fluorescence quantum yields and lifetimes of each of these complexes. In vitro MTT cell viability assay on B16F10 cancer cells revealed that the complexes possibly have a tumoricidal role. The metal-nitrite complexes evidenced the dichotomous NO nature: at high concentration, NO exerted a tumoricidal effect, whereas cancer cells grew at low NO concentration. Flow cytometry or fluorescence microscopy aided cellular uptake calculation. Cell staining followed by fluorescence microscopy associated with organelle markers such as DAPI and Rhodamine 123 detected preferential intracellular localization of the ruthenium-nitrite py-bodipy and aminopropyl lactose derivative ruthenium complex in mitochondria. Thus, the cytotoxicity of compounds (I) and (II) against B16F10 cancer cell line show concentration-dependent results. The present studies suggest that nitric oxide ruthenium derivative compounds could be new potential chemotherapeutic agents against cytotoxic cells.
这项工作研究了发光钌亚硝配合物 cis-Ru(py-bodipy)(dcbpy)(NO) (I) 和 cis-Ru(py-bodipy)(dcbpy-aminopropyl-β-lactose)(NO) (II) 对黑色素瘤细胞系 B16F10 的作用。通过 UV-可见和 FTIR 光谱、MALDI、HPLC 和 H NMR 分析了合成配合物的化学结构和纯度。光谱荧光有助于确定每个配合物的荧光量子产率和寿命。体外 MTT 细胞活力测定法在 B16F10 癌细胞上表明,这些配合物可能具有杀肿瘤作用。金属-亚硝配合物证明了 NO 的二分性质:在高浓度下,NO 发挥杀肿瘤作用,而癌细胞在低浓度的 NO 下生长。流式细胞术或荧光显微镜辅助细胞摄取计算。细胞染色后用荧光显微镜结合细胞器标记物(如 DAPI 和 Rhodamine 123)检测到,线粒体中优先定位了钌-亚硝配合物 py-bodipy 和 aminopropyl lactose 衍生物的钌配合物。因此,化合物 (I) 和 (II) 对 B16F10 癌细胞系的细胞毒性表现出浓度依赖性结果。本研究表明,一氧化氮钌衍生物化合物可能是针对细胞毒性细胞的新型潜在化疗药物。