Design and synthesis of visible light-activatable photocaged peroxides for optical control of ROS-mediated cellular signaling

IF 3.3 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Bioorganic & Medicinal Chemistry Pub Date : 2024-07-27 DOI:10.1016/j.bmc.2024.117863

Mieko Tsuji, Nobuyuki Koiso, Yufu Nishimura, Haruno Taira, Chinami Ogawa, Tasuku Hirayama, Hideko Nagasawa

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Abstract

We designed and synthesized two novel photocaged peroxide compounds, N5TBHP and N6TBHP, featuring nitrogen-containing fused ring coumarin skeletons. Notably, a tetrahydroquinoline fused coumarin derivative, N6TBHP demonstrated significantly higher photocleavage efficiency under visible light at 455 nm compared to N5TBHP, which contains an indoline fused coumarin. This process effectively releases the oxidative stress inducer tert-butylhydroperoxide (TBHP). Additionally, N6TBHP exhibits high resistance to glutathione (GSH), and its UV spectral analysis suggests enhanced intracellular stability due to reduced reactivity with GSH through self-assembly. Furthermore, N6TBHP can release an optimal amount of TBHP into cells under visible light irradiation with minimal cell damage. These properties position N6TBHP as a promising tool for advancing research in intracellular redox signaling.

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设计和合成可见光可激活的光笼型过氧化物，用于对 ROS 介导的细胞信号进行光学控制

我们设计并合成了两种新型光致过氧化物化合物 N5TBHP 和 N6TBHP，它们都以含氮融合环香豆素为骨架。值得注意的是，与含有吲哚啉融合香豆素的 N5TBHP 相比，四氢喹啉融合香豆素衍生物 N6TBHP 在 455 纳米可见光下的光解效率明显更高。这一过程可有效释放氧化应激诱导剂叔丁基过氧化氢（TBHP）。此外，N6TBHP 对谷胱甘肽（GSH）具有很强的抗性，其紫外光谱分析表明，由于通过自组装降低了与 GSH 的反应性，N6TBHP 的细胞内稳定性得到了增强。此外，在可见光照射下，N6TBHP 可以向细胞释放适量的 TBHP，而对细胞的损伤极小。这些特性使 N6TBHP 成为推进细胞内氧化还原信号研究的一种有前途的工具。

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来源期刊

Bioorganic & Medicinal Chemistry 医学-生化与分子生物学

CiteScore

6.80

自引率

2.90%

发文量

413

审稿时长

17 days

期刊介绍： Bioorganic & Medicinal Chemistry provides an international forum for the publication of full original research papers and critical reviews on molecular interactions in key biological targets such as receptors, channels, enzymes, nucleotides, lipids and saccharides. The aim of the journal is to promote a better understanding at the molecular level of life processes, and living organisms, as well as the interaction of these with chemical agents. A special feature will be that colour illustrations will be reproduced at no charge to the author, provided that the Editor agrees that colour is essential to the information content of the illustration in question.