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

Abstract

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 Aβ25-35-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 Aβ25-35-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 Aβ25-35-induced PC12 cells. In addition, our findings demonstrated that compound 5c protected PC12 cells from Aβ25-35-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.

DBU-Promoted Deaminative Thiolation of 1H-Benzo[d]imidazol-2-amines and Benzo[d]oxazol-2-amines

“…Pale yellow solid: 86% yield (41.3 mg, 0.17 mmol); m.p. 48−49 °C; IR (KBr, cm −1 ) 3063, 2978, 2926, 2856, 1600, 1503, 1470, 1427, 1337, 1236, 1212, 1145, 1095, 1073, 927, 860, 6,152.0,142.0,136.0,129.2,128.9,128.0,124.4,124.0,118.6,110.0,36.7;MS (EI,70 eV) m/z 241,225,207,194,180,163,149,131,122,91,thio)benzo [d]oxazole (7b). 29 Eluent: petroleum ether/ethyl acetate (v/v = 20:1).…”

“…For example, compound ( I ) and compound ( II ) are used as antiprotozoal and antihelminthic agents in the field of antiparasitic infections, respectively (Figure ). Compound ( III ) is a selective CRTh2 receptor antagonist for the treatment of asthma and inflammatory diseases, and compound ( IV ) is a potent antialzheimer agent . In addition, compound ( V ) shows potential anticonvulsant activity, and compound ( VI ) exhibits selective activity against the MCF-7 breast cancer cell line …”

“…4 Compound (III) is a selective CRTh2 receptor antagonist for the treatment of asthma and inflammatory diseases, 5 and compound (IV) is a potent antialzheimer agent. 6 In addition, compound (V) shows potential anticonvulsant activity, 7 and compound (VI) exhibits selective activity against the MCF-7 breast cancer cell line. 8 In previous reports, numerous synthetic strategies have been developed to access these two classes of N-heterocycles.…”

Synthesis, Spectral Characteristics, and Molecular Docking Studies of 2,4-Dichloro-N-(2,2,2-trichloro-1-((5-(phenylamino)-1,3,4-thiadiazol-2-yl)amino)ethyl)benzamide

“…These compounds are of particular interest as biologically active compounds [2]. Among the derivatives of 1,3,4-thiadiazole are substances with antitumor [3][4][5][6][7][8][9][10][11], antiviral [11][12][13][14][15][16][17], antimicrobial [10,[18][19][20][21][22][23][24][25][26][27][28][29][30], antioxidant [29,30], neuroprotective [31], antiprotozoal [32], and anti-inflammatory [33,34] activity. In addition, these substances act as inhibitors of acetylcholinesterase [35,36], αglucosidase [37], and carbonic anhydrase [38].…”