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

ABSTRACT: A series of novel synthetic substituted benzo[d]oxazole-based derivatives (5a-5v) exerted neuroprotective effects on ?-amyloid (A?)-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 A?_25-35-induced PC12 cells at 5 ?g/mL. We found that compound 5c was non-neurotoxic at 30 ?g/mL and significantly increased the viability of A?_25-35-induced PC12 cells at 1.25, 2.5 and 5 ?g/mL. Western blot analysis showed that compound 5c promoted the phosphorylation of Akt and glycogen synthase kinase (GSK-3?) and decreased the expression of nuclear factor-?B (NF-?B) in A?_25-35-induced PC12 cells. In addition, our findings demonstrated that compound 5c protected PC12 cells from A?_25-35-induced apoptosis and reduced the hyperphosphorylation of tau protein, and decreased the expression of receptor for AGE (RAGE), ?-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-3?/NF-?B signaling pathway. In vivo studies suggest that compound 5c shows less toxicity than donepezil in the heart and nervous system of zebrafish.

SUBMITTER: Liu Z 

PROVIDER: S-EPMC7698601 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature