A Fluorogenic ONOO--Triggered Carbon Monoxide Donor for Mitigating Brain Ischemic Damage

被引：54

作者：

Xing, Linfeng ^{[1
]}

Wang, Bin ^{[2
,3
]}

Li, Jin ^{[1
]}

Guo, Xinjian ^{[2
]}

Lu, Xicun ^{[1
]}

Chen, Xiaohua ^{[1
]}

Sun, Haitao ^{[4
]}

Sun, Zhenrong ^{[4
]}

Luo, Xiao ^{[5
]}

Qi, Suhua ^{[2
,3
]}

Qian, Xuhong ^{[1
,5
]}

Yang, Youjun ^{[1
]}

机构：

[1] East China Univ Sci & Technol, Sch Pharm, State Key Lab Bioreactor Engn, Shanghai Key Lab Chem Biol, Shanghai 200237, Peoples R China

[2] Xuzhou Med Univ, Sch Med Technol, Xuzhou Key Lab Lab Diagnost, Xuzhou 221004, Jiangsu, Peoples R China

[3] Xuzhou Med Univ, Dept Lab Med, Affiliated Hosp, Xuzhou 221004, Jiangsu, Peoples R China

[4] East China Normal Univ, Sch Phys & Elect Sci, State Key Lab Precis Spect, Shanghai 200241, Peoples R China

[5] East China Normal Univ, Shanghai Engn Res Ctr Mol Therapeut & New Drug De, Sch Chem & Mol Engn, Shanghai 200241, Peoples R China

来源：

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY | 2022年 / 144卷 / 05期

基金：

中国博士后科学基金; 中国国家自然科学基金;

关键词：

IN-SITU; PEROXYNITRITE; THERAPEUTICS; IDENTIFICATION; ANTIOXIDANTS; COMBINATION; MECHANISMS; LIGHT;

D O I：

10.1021/jacs.2c00094

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

Ischemia-reperfusion (I/R) injuries are from the secondary radicals of ONOO-. Direct radical scavenging is difficult because of their high reactivity. ONOO- is longer-lived than the radicals in the biological milieu. Scavenging ONOO- suppresses radical generation preventively. CO is neuroprotective during ischemia. With the scaffold of carbon-caged xanthene, we designed an OONO--triggered CO donor (PCOD585). Notably, PCOD585 exhibited a concomitant fluorescence turn-on upon ONOO- detection, facilitating microscopic monitoring. PCOD585 was cytoprotective in oxygen-glucose deprivation (OGD)-insulted PC-12 cells. It was permeable to the blood-brain barrier and further exhibited neuroprotective effects to MCAO rats by reducing infarction volume, cell apoptosis, and brain edema.

引用

页码：2114 / 2119

页数：6

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