Aly Hanan F, Fouad Ghadha Ibrahim, Khalil Wagdy K B, Kamel Nahla N, El-Rigal Nagy S, Ahmed Kawkab A, Taha Dalia A, Shalaby Mohamed B, Abd El-Karim Somaia S, Abou Baker Doha H, Rizk Maha Z
Department of Therapeutic Chemistry, Pharmaceutical and Drug Industries Research Institute, National Research Centre, Cairo, Egypt.
Department of Cell Biology, National Research Centre, Cairo, Egypt.
Neurol Res. 2025 Jun 21:1-15. doi: 10.1080/01616412.2025.2520021.
Alzheimer's disease (AD) is a progressive age-related neurodegenerative disorder. There is currently no promising cure for AD; the available treatments can only alleviate the symptoms.
The Benzofuran-Enaminone derivative '(E)-1-(benzofuran-2-yl)-3-((2-hydroxyphenyl)amino)prop-2-en-1-one (5)' was synthesized as a potential anti-AD candidate in Aluminum chloride (AlCl)-induced AD in rats.
In vivo and in vitro acute and chronic studies were conducted to examine the potential toxicity, as well as the antioxidant and anti-acetylcholinesterase (AChE) activities of compound 5. Then, rats were divided into four groups: (1) negative control; (2) AD-induced rats; (3) AD-induced rats treated with compound 5; and (4) AD-induced rats treated with Donepezil. Behavioral, biochemical, and molecular investigations were conducted. The expression of insulin 1 gene, apoptotic genes, and the AD-related genes were estimated.
The selected dose of compound 5 (10 mg/kg) was based on an acute toxicity test, then it was applied for a chronic study for 1 month; no toxicological features were stimulated. In vitro, compound 5 demonstrated antioxidant and anti-AChE activities. The expression of apoptotic genes (Bcl-2, Bax, and Caspase-3), AD-related genes (Amyloid precursor protein (APP) and Tau), and the insulin 1 gene were altered in AD-induced rats versus control rats. Treatment of AD rats with compound 5 counteracted the AlCl-induced neurotoxicity.
This study could be regarded as an initial step in drug discovery for testing this new chemical entity as a potent anti-AD therapeutic agent.
阿尔茨海默病（AD）是一种与年龄相关的进行性神经退行性疾病。目前尚无有望治愈AD的方法；现有的治疗只能缓解症状。
合成苯并呋喃-烯胺酮衍生物“(E)-1-(苯并呋喃-2-基)-3-((2-羟基苯基)氨基)丙-2-烯-1-酮（5）”，作为大鼠氯化铝（AlCl）诱导的AD的潜在抗AD候选药物。
进行体内和体外的急性和慢性研究，以检测化合物5的潜在毒性以及抗氧化和抗乙酰胆碱酯酶（AChE）活性。然后，将大鼠分为四组：（1）阴性对照组；（2）AD诱导组；（3）用化合物5治疗的AD诱导组；（4）用多奈哌齐治疗的AD诱导组。进行行为、生化和分子研究。评估胰岛素1基因、凋亡基因和AD相关基因的表达。
根据急性毒性试验选择化合物5的剂量（10 mg/kg），然后将其用于为期1个月的慢性研究；未引发毒理学特征。在体外，化合物5表现出抗氧化和抗AChE活性。与对照大鼠相比，AD诱导大鼠中凋亡基因（Bcl-2、Bax和Caspase-3）、AD相关基因（淀粉样前体蛋白（APP）和Tau）以及胰岛素1基因的表达发生了改变。用化合物5治疗AD大鼠可抵消AlCl诱导的神经毒性。
本研究可被视为药物发现的第一步，用于测试这种新化学实体作为一种有效的抗AD治疗剂。
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