Alzheimer's disease (AD) and type 2 diabetes (T2D) are common diseases in the elderly, and the increasing number of patients with these diseases has become a serious health problem worldwide. The aggregation and development of plaque of amyloid polypeptides (amyloid β; Aβ and human islet amyloid polypeptide; hIAPP, amylin) are found in the brains of patients with AD and the pancreas of patients with T2D and are considered to be, in part, the causes of both diseases, respectively. Therefore, preventing amyloid aggregation may be a promising therapeutic strategy for preventing AD and T2D. In addition, the disaggregation of the already aggregated amyloid polypeptides is expected to contribute to the prevention and treatment of both diseases as amyloid polypeptide aggregations begin several decades before the onset of disease. Therefore, in this study, we investigated the hIAPP aggregation inhibitory activity and Aβ42/hIAPP disaggregation activity of clovamide which had shown inhibitory activity against Aβ42 aggregation in our previous studies. In addition, active sites were identified (structure–activity relationship analysis) using clovamide-related compounds in which hydroxyl groups of these compounds were either eliminated or methylated. Our results showed that the compounds with one or two catechol moieties showed strong hIAPP aggregation inhibitory activity and Aβ42/hIAPP disaggregation activity; and the non-catechol type compounds showed little or no activity. This suggests that the catechol moiety is important in amyloid polypeptide aggregation inhibition and disaggregation. Thus, clovamide and its related compounds may be promising therapeutic strategies for inhibiting amyloid polypeptide-related pathology in AD and T2D.

阿尔茨海默氏病（AD）和2型糖尿病（T2D）是老年人的常见疾病，越来越多的患有这些疾病的患者已成为全球范围内的严重健康问题。在AD患者的大脑和T2D患者的胰腺中发现了淀粉样多肽（淀粉样β；Aβ和人胰岛淀粉样多肽； hIAPP，淀粉样蛋白）的斑块的聚集和发育。两种疾病的病因分别。因此，预防淀粉样蛋白聚集可能是预防AD和T2D的有前途的治疗策略。另外，由于淀粉样多肽的聚集在疾病发作之前的几十年开始，因此预期已经聚集的淀粉样多肽的分解将有助于两种疾病的预防和治疗。因此，在这项研究中，我们调查了氯乙烯酰胺的hIAPP聚集抑制活性和Aβ42/ hIAPP分解活性，这些活性在我们以前的研究中显示出对Aβ42聚集的抑制活性。此外，使用氯乙烯酰胺相关的化合物识别了活性位点（结构-活性关系分析），其中这些化合物的羟基被消除或甲基化。我们的结果表明，具有一个或两个邻苯二酚部分的化合物显示出强大的hIAPP聚集抑制活性和Aβ42/ hIAPP分解活性。非儿茶酚类化合物几乎没有活性。这表明邻苯二酚部分在淀粉样多肽聚集抑制和分解中很重要。从而，