In the last few decades, Alzheimer’s disease (AD) has emerged as a serious global problem, and it has been considered as the most common type of dementia. PPARγ and beta-secretase 1 (BACE1) are considered as potential targets for Alzheimer’s disease management. In the same time, sulfonylureas and sulfonamides have been confirmed to have PPARγ agonistic activity. Aiming to obtain new anti-AD agents, thirty-five compounds of sulfonamide and sulfonylurea derivatives having the same essential pharmacophoric features of the reported PPARγ agonists have been subjected to virtual screening. Docking studies revealed that five compounds (1, 2, 3, 4, and 5) have promising affinities to PPARγ. They were also docked into the binding site of BACE1. In addition, ADMET and physicochemical properties of these compounds were considered. Additionally, these compounds were further evaluated against BACE1 and PPARγ. Compound 2 showed IC50 value of 1.64 μM against BACE1 and EC50 value of 0.289 μM against PPARγ.

中文翻译：

---

筛选一些磺酰胺和磺酰脲类衍生物作为靶向 BACE1 和 PPARγ 的抗阿尔茨海默病药物

在过去的几十年中，阿尔茨海默病 (AD) 已成为一个严重的全球性问题，并被认为是最常见的痴呆症类型。PPARγ 和 β-分泌酶 1 (BACE1) 被认为是阿尔茨海默病管理的潜在目标。同时，磺酰脲类和磺胺类药物已被证实具有 PPARγ 激动活性。为了获得新的抗 AD 药物，对 35 种磺酰胺和磺酰脲衍生物的化合物进行了虚拟筛选，这些化合物具有与报道的 PPARγ 激动剂相同的基本药效特征。对接研究表明，五种化合物（1、2、3、4 和 5）对 PPARγ 具有良好的亲和力。它们还停靠在 BACE1 的结合位点上。此外，还考虑了这些化合物的 ADMET 和理化性质。此外，这些化合物针对 BACE1 和 PPARγ 进行了进一步评估。化合物 2 对 BACE1 的 IC50 值为 1.64 μM，对 PPARγ 的 EC50 值为 0.289 μM。