Alzheimer's disease (AD) is a severe age dependent and chronic problem with no cure so far. The available treatments are temporary, acting over short period of time. The main pathological hallmark of the disease includes cholinergic dysfunction, oxidative stress, accumulation of Aβ fibrils and tau tangles. In context with the multi-factorial nature of this disease, two different series of molecules were developed to hit the multifactorial disease targets. Mainly, the molecules were designed to inhibit the AChE and aggregation of Aβ, and also oxidative damage. Two novel series of TAC-fenbufen/menbutone conjugated molecules were designed, synthesized and bio-assayed. All compounds showed inhibition capacity towards AChE, Aβ aggregation and moderate to good radical scavenging capacity. Particularly, five TAC-menbutone molecules showed improved AChE and Aβ aggregation inhibition capacity compared to TAC-fenbufen conjugated molecules. Overall, these novel series of molecules may be potential drug lead molecules in the treatment of AD.

中文翻译：

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具有胆碱酯酶和淀粉样蛋白-β 抑制活性的多靶向他克林缀合物：新的抗阿尔茨海默氏症药物

阿尔茨海默病 (AD) 是一种严重的年龄依赖性和慢性问题，迄今为止无法治愈。可用的治疗是暂时的，在短时间内起作用。该疾病的主要病理特征包括胆碱能功能障碍、氧化应激、Aβ 原纤维的积聚和 tau 缠结。在这种疾病的多因素性质的背景下，开发了两种不同系列的分子来达到多因素疾病的目标。主要是，这些分子旨在抑制 AChE 和 Aβ 的聚集，以及氧化损伤。设计、合成和生物测定了两个新系列的 TAC-芬布芬/门布酮偶联分子。所有化合物均显示出对 AChE、Aβ 聚集的抑制能力和中等至良好的自由基清除能力。特别，与 TAC-芬布芬偶联分子相比，五种 TAC-门布酮分子显示出改善的 AChE 和 Aβ 聚集抑制能力。总的来说，这些新的分子系列可能是治疗 AD 的潜在药物先导分子。