依达拉奉
过氧亚硝酸盐
三氟甲基
化学
血脑屏障
荧光
药理学
生物物理学
神经科学
生物化学
医学
有机化学
生物
中枢神经系统
烷基
物理
量子力学
酶
超氧化物
作者
Lei Shen,Hongmei Liu,Ming Jin,Jinchao Zhang,Caixia Yin,Shuxiang Wang,Yutao Yang
标识
DOI:10.1016/j.cclet.2024.109572
摘要
Epilepsy, as a chronic neurological disease of the brain, is closely related to oxidative stress, and the peroxynitrite (ONOO−) significantly rise up in this event. Therefore, ONOO− is considered as a potential biomarker for early prediction of epilepsy. However, some potential diagnostic reagents for epilepsy are hindered by the blood-brain barrier (BBB). Meanwhile, "drug repurposing" is attracting a growing interest. Edaravone (EDA), as a first-line drug in the clinical treatment of cerebral ischemia, plays antioxidant roles in scavenging free radicals, promising potential antiepileptic activity. Thus, it is imperative to develop fluorescent probes for monitoring ONOO− fluctuations in the epileptic brain. Hence, we proposed a novel fluorescent probe with the thiocarbonate as the promising recognition unit for ONOO− and dicyanoisophorone derivative as the fluorophore. Moreover, by the "three-in-one" strategy, the introduction of trifluoromethyl into DCI-ONOO-3 can extend the emission wavelength of the fluorophore, shorten the response and increase lipophilicity. Consequently, DCI-ONOO-3 was used for monitoring ONOO− fluxes in brain of epileptic mice and evaluating the antiepileptic efficacy of EDA. It opens up a new way for the design of BBB permeable fluorescent probes, and provides a convincing new method for the diagnosis and treatment of epilepsy.
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