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 (<b>5a</b>–<b>5v</b>) 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 s...
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/25/22/5391 |
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doaj-358887c9e7304ad5a0e559eb920be6462020-11-25T04:01:45ZengMDPI AGMolecules1420-30492020-11-01255391539110.3390/molecules25225391Design and Synthesis of New Benzo[d]oxazole-Based Derivatives and Their Neuroprotective Effects on β-Amyloid-Induced PC12 CellsZheng Liu0Ming Bian1Qian-qian Ma2Zhuo Zhang3Huan-huan Du4Cheng-xi Wei5Medicinal Chemistry and Pharmacology Institute, Inner Mongolia University for the Nationalities, Tongliao 028000, ChinaMedicinal Chemistry and Pharmacology Institute, Inner Mongolia University for the Nationalities, Tongliao 028000, ChinaMedicinal Chemistry and Pharmacology Institute, Inner Mongolia University for the Nationalities, Tongliao 028000, ChinaCollege of Pharmaceutical Sciences, Yanbian University, Yanji 133022, ChinaMedicinal Chemistry and Pharmacology Institute, Inner Mongolia University for the Nationalities, Tongliao 028000, ChinaMedicinal Chemistry and Pharmacology Institute, Inner Mongolia University for the Nationalities, Tongliao 028000, ChinaA series of novel synthetic substituted benzo[d]oxazole-based derivatives (<b>5a</b>–<b>5v</b>) 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<sub>25-35</sub>-induced PC12 cells at 5 μg/mL. We found that compound <b>5c</b> was non-neurotoxic at 30 μg/mL and significantly increased the viability of Aβ<sub>25-35</sub>-induced PC12 cells at 1.25, 2.5 and 5 μg/mL. Western blot analysis showed that compound <b>5c</b> promoted the phosphorylation of Akt and glycogen synthase kinase (GSK-3β) and decreased the expression of nuclear factor-κB (NF-κB) in Aβ<sub>25-35</sub>-induced PC12 cells. In addition, our findings demonstrated that compound <b>5c</b> protected PC12 cells from Aβ<sub>25-35</sub>-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 <b>5c</b> shows less toxicity than donepezil in the heart and nervous system of zebrafish.https://www.mdpi.com/1420-3049/25/22/5391synthesisbenzo[d]oxazolthiadiazolesAlzheimer’s diseaseβ-amyloidAkt/GSK-3β/NF-κB signaling pathway |
| collection |
DOAJ |
| language |
English |
| format |
Article |
| sources |
DOAJ |
| author |
Zheng Liu Ming Bian Qian-qian Ma Zhuo Zhang Huan-huan Du Cheng-xi Wei |
| spellingShingle |
Zheng Liu Ming Bian Qian-qian Ma Zhuo Zhang Huan-huan Du Cheng-xi Wei Design and Synthesis of New Benzo[d]oxazole-Based Derivatives and Their Neuroprotective Effects on β-Amyloid-Induced PC12 Cells Molecules synthesis benzo[d]oxazol thiadiazoles Alzheimer’s disease β-amyloid Akt/GSK-3β/NF-κB signaling pathway |
| author_facet |
Zheng Liu Ming Bian Qian-qian Ma Zhuo Zhang Huan-huan Du Cheng-xi Wei |
| author_sort |
Zheng Liu |
| title |
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_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_sort |
design and synthesis of new benzo[d]oxazole-based derivatives and their neuroprotective effects on β-amyloid-induced pc12 cells |
| publisher |
MDPI AG |
| series |
Molecules |
| issn |
1420-3049 |
| publishDate |
2020-11-01 |
| description |
A series of novel synthetic substituted benzo[d]oxazole-based derivatives (<b>5a</b>–<b>5v</b>) 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<sub>25-35</sub>-induced PC12 cells at 5 μg/mL. We found that compound <b>5c</b> was non-neurotoxic at 30 μg/mL and significantly increased the viability of Aβ<sub>25-35</sub>-induced PC12 cells at 1.25, 2.5 and 5 μg/mL. Western blot analysis showed that compound <b>5c</b> promoted the phosphorylation of Akt and glycogen synthase kinase (GSK-3β) and decreased the expression of nuclear factor-κB (NF-κB) in Aβ<sub>25-35</sub>-induced PC12 cells. In addition, our findings demonstrated that compound <b>5c</b> protected PC12 cells from Aβ<sub>25-35</sub>-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 <b>5c</b> shows less toxicity than donepezil in the heart and nervous system of zebrafish. |
| topic |
synthesis benzo[d]oxazol thiadiazoles Alzheimer’s disease β-amyloid Akt/GSK-3β/NF-κB signaling pathway |
| url |
https://www.mdpi.com/1420-3049/25/22/5391 |
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