Institute of Materia Medica, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, China.
J Enzyme Inhib Med Chem. 2021 Dec;36(1):450-461. doi: 10.1080/14756366.2021.1873978.
Rheumatoid arthritis is a chronic systemic disease characterised by an unknown aetiology of inflammatory synovitis. A large number of studies have shown that synoviocytes show tumour-like dysplasia in the pathological process of RA, and the changes in the expression of related cytokines are closely related to the pathogenesis of RA. In this thesis, a series of novel 3-(4-aminophenyl) coumarins containing different substituents were synthesised to find new coumarin anti-inflammatory drugs for the treatment of rheumatoid arthritis. The results of preliminary activity screening showed that compound had the strongest inhibitory activity on the proliferation of fibroid synovial cells, and it also had inhibitory effect on RA-related cytokines IL-1, IL-6, and TNF-α. The preliminary mechanism study showed that compound could inhibit the activation of NF-κB and MAPKs signal pathway. The anti-inflammatory activity of compound was further determined in the rat joint inflammation model.
类风湿关节炎是一种慢性全身性疾病，其特征为炎症性滑膜炎的病因不明。大量研究表明，滑膜细胞在 RA 的病理过程中表现出肿瘤样异型增生，相关细胞因子的表达变化与 RA 的发病机制密切相关。在本论文中，设计并合成了一系列含有不同取代基的新型 3-(4-氨基苯基)香豆素，以寻找新的香豆素类抗炎药物来治疗类风湿关节炎。初步活性筛选结果表明，化合物 对纤维样滑膜细胞的增殖具有最强的抑制活性，并且对 RA 相关细胞因子 IL-1、IL-6 和 TNF-α也具有抑制作用。初步的机制研究表明，化合物 可以抑制 NF-κB 和 MAPKs 信号通路的激活。在大鼠关节炎症模型中进一步确定了化合物 的抗炎活性。
