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Design and Synthesis of New Benzo[d]oxazole-Based Derivatives and Their Neuroprotective Effects on β-Amyloid-Induced PC12 Cells

A series of novel synthetic substituted benzo[d]oxazole-based derivatives (5a–5v) exerted neuroprotective effects on β-amyloid (Aβ)-induced PC12 cells as a potential approach for the treatment of Alzheimer’s disease (AD). In vitro studies show that most of the synthesized compounds were potent in re...

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Autores principales: Liu, Zheng, Bian, Ming, Ma, Qian-Qian, Zhang, Zhuo, Du, Huan-Huan, Wei, Cheng-Xi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7698601/
https://www.ncbi.nlm.nih.gov/pubmed/33218007
http://dx.doi.org/10.3390/molecules25225391
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author Liu, Zheng
Bian, Ming
Ma, Qian-Qian
Zhang, Zhuo
Du, Huan-Huan
Wei, Cheng-Xi
author_facet Liu, Zheng
Bian, Ming
Ma, Qian-Qian
Zhang, Zhuo
Du, Huan-Huan
Wei, Cheng-Xi
author_sort Liu, Zheng
collection PubMed
description A series of novel synthetic substituted benzo[d]oxazole-based derivatives (5a–5v) exerted neuroprotective effects on β-amyloid (Aβ)-induced PC12 cells as a potential approach for the treatment of Alzheimer’s disease (AD). In vitro studies show that most of the synthesized compounds were potent in reducing the neurotoxicity of Aβ(25-35)-induced PC12 cells at 5 μg/mL. We found that compound 5c was non-neurotoxic at 30 μg/mL and significantly increased the viability of Aβ(25-35)-induced PC12 cells at 1.25, 2.5 and 5 μg/mL. Western blot analysis showed that compound 5c promoted the phosphorylation of Akt and glycogen synthase kinase (GSK-3β) and decreased the expression of nuclear factor-κB (NF-κB) in Aβ(25-35)-induced PC12 cells. In addition, our findings demonstrated that compound 5c protected PC12 cells from Aβ(25-35)-induced apoptosis and reduced the hyperphosphorylation of tau protein, and decreased the expression of receptor for AGE (RAGE), β-site amyloid precursor protein (APP)-cleaving enzyme 1 (BACE1), inducible nitric oxide synthase (iNOS) and Bcl-2-associated X protein/B-cell lymphoma 2 (Bax/Bcl-2) via Akt/GSK-3β/NF-κB signaling pathway. In vivo studies suggest that compound 5c shows less toxicity than donepezil in the heart and nervous system of zebrafish.
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spelling pubmed-76986012020-11-29 Design and Synthesis of New Benzo[d]oxazole-Based Derivatives and Their Neuroprotective Effects on β-Amyloid-Induced PC12 Cells Liu, Zheng Bian, Ming Ma, Qian-Qian Zhang, Zhuo Du, Huan-Huan Wei, Cheng-Xi Molecules Article A series of novel synthetic substituted benzo[d]oxazole-based derivatives (5a–5v) exerted neuroprotective effects on β-amyloid (Aβ)-induced PC12 cells as a potential approach for the treatment of Alzheimer’s disease (AD). In vitro studies show that most of the synthesized compounds were potent in reducing the neurotoxicity of Aβ(25-35)-induced PC12 cells at 5 μg/mL. We found that compound 5c was non-neurotoxic at 30 μg/mL and significantly increased the viability of Aβ(25-35)-induced PC12 cells at 1.25, 2.5 and 5 μg/mL. Western blot analysis showed that compound 5c promoted the phosphorylation of Akt and glycogen synthase kinase (GSK-3β) and decreased the expression of nuclear factor-κB (NF-κB) in Aβ(25-35)-induced PC12 cells. In addition, our findings demonstrated that compound 5c protected PC12 cells from Aβ(25-35)-induced apoptosis and reduced the hyperphosphorylation of tau protein, and decreased the expression of receptor for AGE (RAGE), β-site amyloid precursor protein (APP)-cleaving enzyme 1 (BACE1), inducible nitric oxide synthase (iNOS) and Bcl-2-associated X protein/B-cell lymphoma 2 (Bax/Bcl-2) via Akt/GSK-3β/NF-κB signaling pathway. In vivo studies suggest that compound 5c shows less toxicity than donepezil in the heart and nervous system of zebrafish. MDPI 2020-11-18 /pmc/articles/PMC7698601/ /pubmed/33218007 http://dx.doi.org/10.3390/molecules25225391 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Liu, Zheng
Bian, Ming
Ma, Qian-Qian
Zhang, Zhuo
Du, Huan-Huan
Wei, Cheng-Xi
Design and Synthesis of New Benzo[d]oxazole-Based Derivatives and Their Neuroprotective Effects on β-Amyloid-Induced PC12 Cells
title Design and Synthesis of New Benzo[d]oxazole-Based Derivatives and Their Neuroprotective Effects on β-Amyloid-Induced PC12 Cells
title_full Design and Synthesis of New Benzo[d]oxazole-Based Derivatives and Their Neuroprotective Effects on β-Amyloid-Induced PC12 Cells
title_fullStr Design and Synthesis of New Benzo[d]oxazole-Based Derivatives and Their Neuroprotective Effects on β-Amyloid-Induced PC12 Cells
title_full_unstemmed Design and Synthesis of New Benzo[d]oxazole-Based Derivatives and Their Neuroprotective Effects on β-Amyloid-Induced PC12 Cells
title_short Design and Synthesis of New Benzo[d]oxazole-Based Derivatives and Their Neuroprotective Effects on β-Amyloid-Induced PC12 Cells
title_sort design and synthesis of new benzo[d]oxazole-based derivatives and their neuroprotective effects on β-amyloid-induced pc12 cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7698601/
https://www.ncbi.nlm.nih.gov/pubmed/33218007
http://dx.doi.org/10.3390/molecules25225391
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