Citation: Chengcheng Zhang, Zhe Wu, Ningning Jiang, Yi Song, Weina Geng, Hongmei Liu, Ming Jin, Shuxiang Wang, Jinchao Zhang, Yutao Yang. A fluorescent probe regulated by trifluoromethyl and nitrogen-containing heterocycles for monitoring biothiol fluctuations in the brains of mice with schizophrenia[J]. Chinese Chemical Letters, ;2026, 37(1): 111476. doi: 10.1016/j.cclet.2025.111476 shu

A fluorescent probe regulated by trifluoromethyl and nitrogen-containing heterocycles for monitoring biothiol fluctuations in the brains of mice with schizophrenia

Chengcheng Zhang ^{a, 1} ,
Zhe Wu ^{a, 1} ,
Ningning Jiang ^a ,
Yi Song ^b ,
Weina Geng ^a ,
Hongmei Liu ^a ,
Ming Jin ^a ,
Shuxiang Wang ^{a, *,} ,
Jinchao Zhang ^a ,
Yutao Yang ^{a, *,}

a.
Key Laboratory of Medicinal Chemistry and Molecular Diagnosis of the Ministry of Education, Chemical Biology Key Laboratory of Hebei Province, State Key Laboratory of New Pharmaceutical Preparations and Excipients, College of Chemistry and Materials Science, Hebei University, Baoding 071002, China
b.
College of Pharmaceutical Science, Hebei University, Baoding 071002, China

wsx@hbu.edu.cn

yutaoyang2016@163.com

Received Date: 7 May 2025
Revised Date: 10 June 2025
Accepted Date: 15 June 2025
Available Online: 16 June 2025

Figures(4)

Schizophrenia (SCZ) is a severe mental disorder with an unclear pathogenesis. Increasing evidence suggests that oxidative stress (OS) may contribute to the neuropathological processes underlying SCZ. Biothiols, key endogenous antioxidants, have been proposed as potential biomarkers for the disease. However, due to the presence of the blood-brain barrier (BBB), fluorescent probes are rarely used to image biothiols in the brain of SCZ models. In this study, a series of fluorescent probes for biothiols were developed using dicyanoisophorone derivatives as fluorophores known for their excellent optical properties, and carboxylic esters as recognition units. A parallel synthesis and rapid screening strategy was employed to construct and optimize these probes. By introducing trifluoromethyl and benzothiazole groups into the fluorophore, the emission wavelength was successfully shifted into the near-infrared region. Additionally, various trifluoromethyl-substituted aromatic and nitrogen heterocyclic compounds were incorporated to optimize the carboxylic esters, thereby improving the probes' reactivity and lipophilicity. Systematic evaluation of the physicochemical characteristics, and optical performance led to the identification of DCI-BT-11 as the most promising candidate. DCI-BT-11 demonstrated excellent BBB permeability and a good response to biothiols both in vitro and in vivo. Notably, DCI-BT-11 was used for the first time to visualize biothiol flux and assess the therapeutic effects of the antioxidant N-acetylcysteine (NAC) in the brains of SCZ mouse models, offering new insights into the role of OS in the pathogenesis and treatment of SCZ.
- Fluorescent probe,
- Biothiol,
- Blood-brain barrier,
- Schizophrenia,
- Oxidative stress
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