دورية أكاديمية
Novel pyrrolidine-alkylamino-substituted dicyanoisophorone derivatives as near-infrared fluorescence probe for imaging β-amyloid in vitro and in vivo.
| العنوان: | Novel pyrrolidine-alkylamino-substituted dicyanoisophorone derivatives as near-infrared fluorescence probe for imaging β-amyloid in vitro and in vivo. |
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| المؤلفون: | Zhou H; Henan Key Laboratory of Natural Medicine Innovation and Transformation, Henan University, Kaifeng, 475004, China; Pharmaceutical Engineering Department, Henan Technical Institute, Kaifeng, 475004, China., Zhai J; Henan Key Laboratory of Natural Medicine Innovation and Transformation, Henan University, Kaifeng, 475004, China., Gong H; Henan Key Laboratory of Natural Medicine Innovation and Transformation, Henan University, Kaifeng, 475004, China., Fang R; Henan Key Laboratory of Natural Medicine Innovation and Transformation, Henan University, Kaifeng, 475004, China., Zhao Y; Pharmaceutical Engineering Department, Henan Technical Institute, Kaifeng, 475004, China. Electronic address: zhaoyongmei_2004@163.com., Luo W; Henan Key Laboratory of Natural Medicine Innovation and Transformation, Henan University, Kaifeng, 475004, China; State Key Laboratory of Antiviral Drugs, Henan University, Kaifeng 475004, China. Electronic address: luowen83@henu.edu.cn. |
| المصدر: | Analytica chimica acta [Anal Chim Acta] 2024 Aug 15; Vol. 1317, pp. 342894. Date of Electronic Publication: 2024 Jun 20. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Elsevier Country of Publication: Netherlands NLM ID: 0370534 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1873-4324 (Electronic) Linking ISSN: 00032670 NLM ISO Abbreviation: Anal Chim Acta Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: Amsterdam : Elsevier Original Publication: Amsterdam. |
| مواضيع طبية MeSH: | Cyclohexanones*/chemical synthesis , Cyclohexanones*/chemistry , Cyclohexanones*/pharmacology, Humans ; Cell Line ; Amyloid beta-Protein Precursor/analysis ; Amyloid beta-Protein Precursor/chemistry ; Amyloid beta-Protein Precursor/metabolism ; Pyrrolidines/chemistry ; Spectroscopy, Near-Infrared ; Molecular Structure ; Fluorescent Dyes/chemical synthesis ; Fluorescent Dyes/chemistry ; Fluorescent Dyes/pharmacology ; Spectrometry, Fluorescence ; Models, Molecular ; Protein Structure, Tertiary ; Molecular Docking Simulation ; Cell Survival/drug effects ; Animals ; Mice ; Male ; Mice, Inbred C57BL ; Brain/metabolism ; Amination ; Alkylation |
| مستخلص: | Background: The formation of amyloid-β (Aβ) plaques is one of the key neuropathological hallmarks of Alzheimer's disease (AD). Near-infrared (NIR) probes show great potential for imaging of Aβ plaques in vivo and in vitro. Dicyanoisophorone (DCIP) based Aβ probes have attracted considerable attention due to their exceptional properties. However, DCIP probes still has some drawbacks, such as short emission wavelength (<650 nm) and low fluorescence intensity after binding to Aβ. It is clear that further modification is needed to improve their luminescence efficiency and sensitivity. Results: We designed and synthesize four novel pyrrolidine-alkylamino-substituted DCIP derivatives (6a-d) as imaging agents for β-amyloid (Aβ) aggregates. Compound 6c responds better to Aβ aggregates than the other three compounds (6a, 6b and 6d) and its precursor DCIP. The calculated detection limit is to be as low as 0.23 μM. Compound 6c shows no cytotoxicity in the tested concentration for SH-SY5Y and HL-7702 cells. Additionally, compound 6c is successfully applied to monitor Aβ aggregates in live SH-SY5Y cells and APP/PS1 transgenic mice. The retention time in the transgenic mice brain is much longer than that of age-matched wild-type mice. Significance: The results indicates that compound 6c had an excellent ability to penetrate the blood-brain barrier and it could effectively distinguish APP/PS1 transgenic mice and wide-type mice. This represents its promising applications for Aβ detection in basic and biomedical research. Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. (Copyright © 2024 Elsevier B.V. All rights reserved.) |
| فهرسة مساهمة: | Keywords: Alzheimer's disease; Dicyanoisophorone; Fluorescence imaging; β-amyloid |
| المشرفين على المادة: | 0 (Amyloid beta-Protein Precursor) 0 (APP protein, human) LJU5627FYV (pyrrolidine) 0 (Pyrrolidines) 2BR99VR6WA (isophorone) 0 (Cyclohexanones) 0 (Fluorescent Dyes) |
| تواريخ الأحداث: | Date Created: 20240719 Date Completed: 20240723 Latest Revision: 20240723 |
| رمز التحديث: | 20240723 |
| DOI: | 10.1016/j.aca.2024.342894 |
| PMID: | 39030021 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1873-4324 |
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| DOI: | 10.1016/j.aca.2024.342894 |