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新型双苯并咪唑-亚硝酮类化合物可用于活细胞中的核氧化还原成像。

Novel bisbenzimide-nitroxides for nuclear redox imaging in living cells.

机构信息

Graduate School of Pharmaceutical Sciences, Nagoya City University, Tanabe-dori 3-1, Mizuho-ku, Nagoya, Aichi 467-8603, Japan.

出版信息

Bioorg Med Chem Lett. 2012 Mar 1;22(5):1949-52. doi: 10.1016/j.bmcl.2012.01.042. Epub 2012 Jan 24.

Abstract

Nuclear oxidative stress damages genomic DNA and may lead to cell death, leading to aging and aging-related disorders. Though it is important to measure the nuclear oxidative stress separately, there are still little examples that applicable to living cells. We have designed and synthesized three bisbenzimide-nitroxides as probes to selectively visualize nuclear redox changes in terms of fluorescence. Compound 3, containing two radical moieties, showed the largest reduction-induced fluorescence change, with good localization in nuclei. RAW264.7 murine macrophage cells were loaded with compound 3 and then treated with 100μM hydrogen peroxide for 5min to show the fluorescence increase. This fluorescence increase was inhibited by pretreatment of 1mM ascorbic acid. These results show that compound 3 was suitable for nuclear-specific redox imaging in murine macrophages.

摘要

核氧化应激会损害基因组 DNA,可能导致细胞死亡,从而导致衰老和与衰老相关的疾病。虽然分别测量核氧化应激很重要,但仍很少有适用于活细胞的例子。我们设计并合成了三种双苯并咪唑-氮氧化物作为探针,以荧光的方式选择性地可视化核氧化还原变化。含有两个自由基部分的化合物 3 显示出最大的还原诱导荧光变化,并且在核内有良好的定位。用化合物 3 装载 RAW264.7 鼠巨噬细胞,然后用 100μM 过氧化氢处理 5min 以显示荧光增加。用 1mM 抗坏血酸预处理可抑制这种荧光增加。这些结果表明,化合物 3 适用于鼠巨噬细胞中的核特异性氧化还原成像。

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