乌杜拉诺伊德A-D:意想不到的塞斯特特类作为治疗牛皮的强效S100A8/A9复合抑制剂
Yuyi Zheng1, Xiaotian Zhang1, Xiaoxia Gu1
1Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation, School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
Acta pharmaceutica Sinica. B
|January 1, 2026
概括
来自Aspergillus undulatus的新型化合物,undulanoids A-D,显示出治疗牛皮的潜力. 恩杜拉诺伊德B有效抑制S100A9表达和角质细胞的增殖,为这种免疫介导的皮肤疾病提供了一种新的治疗策略.
科学领域:
- 自然产品化学 自然产品化学
- 免疫学 免疫学 免疫学
- 皮肤病学 皮肤病学
背景情况:
- 牛皮是一种具有挑战性的免疫媒介性皮肤疾病,其特点是皮肤上的异常斑块.
- 向S100A8和S100A9分子在角质细胞中是一种有前途的治疗策略.
- S100A8/A9复合体在牛皮的发病过程中起着至关重要的作用.
研究的目的:
- 从*Aspergillus undulatus*中分离和表征新型化合物,这些化合物有可能用于牛皮的治疗.
- 研究这些化合物的作用机制,特别是它们对S100A8/A9.9的影响.
- 在前临床小鼠牛皮病模型中评估最有前途的化合物的治疗疗效.
主要方法:
- 使用光谱数据和单晶X射线衍射,分离和阐明四种新型类类 (undulanoids A-D) 的结构.
- 抑制试验针对瘤亡因子和互白素-17信号通路.
- 反向目标预测,细胞热转移测定,动态模拟和体内疗效研究,在小鼠模型上进行因伊米基莫德诱导的牛皮形皮肤病变.
主要成果:
- 四种新型的sesterterpenoids,undulanoids A-D,被隔离和表征.
- 恩杜拉诺伊德B显著抑制S100A9表达和角质细胞增殖.
- 化合物2有效抑制了S100A8/A9复合体,并在牛皮的小鼠模型中显示出强大的治疗效果.
结论:
- 翁杜拉诺基A-D是一种具有独特的五环环系统的新型氏类.
- 恩杜拉诺伊德B是治疗牛皮的有希望的化合物,因为它有抑制S100A9和角质细胞增殖的能力.
- 这一发现为管理牛皮提供了新的分子支架和潜在的治疗剂.
相关概念视频
01:29Drugs for Treatment of Ulcerative Colitis in IBD
416
Ulcerative colitis is a chronic inflammatory condition primarily affecting the colon and rectum. The primary drugs used in the treatment of ulcerative colitis are aminosalicylates. They exhibit anti-inflammatory and immunosuppressive properties. They modulate inflammatory mediators and inhibit the activity of nuclear factor κB (NF-κB). Aminosalicylates also reduce inflammation by inhibiting prostaglandin and leukotriene production and decreasing neutrophil chemotaxis and superoxide...
416
01:17Drugs for Treatment of Diarrhea-Predominant IBS
593
Diarrhea-predominant irritable bowel syndrome (IBS-D) is a subtype of IBS characterized primarily by frequent, loose, or watery stools, abdominal pain, and abdominal discomfort. Therapeutic approaches to managing IBS-D include dietary changes, stress management techniques, and pharmaceutical interventions.
Two specific drugs used in the treatment are alosetron (Lotronex) and eluxadoline (Viberzi). Alosetron, a 5-HT3 antagonist, works by slowing the movement of stools in the gut, reducing bowel...
Two specific drugs used in the treatment are alosetron (Lotronex) and eluxadoline (Viberzi). Alosetron, a 5-HT3 antagonist, works by slowing the movement of stools in the gut, reducing bowel...
593
01:20Drugs for Peptic Ulcer Disease: Prostaglandin Analogs as Mucosal Protective Agents
1.0K
The gastric mucosa produces prostaglandins E2 (PGE2) and prostacyclin (PGI2), crucial in maintaining gastric health. They exert cytoprotective effects, including increasing bicarbonate secretion, releasing protective mucin, reducing gastric acid output, and preventing harmful vasoconstriction. These effects are mediated through various receptors, such as EP1, EP2, EP3, and EP4.
Non-steroidal anti-inflammatory drugs (NSAIDs) can induce peptic ulcers by inhibiting cyclooxygenase, decreasing...
Non-steroidal anti-inflammatory drugs (NSAIDs) can induce peptic ulcers by inhibiting cyclooxygenase, decreasing...
1.0K
01:19Antiasthma Drugs: Leukotriene Modifiers
1.7K
Leukotriene modifiers, or cysteinyl leukotriene receptor antagonists, are medications used to manage chronic asthma. These agents target specific inflammatory mediators produced during arachidonic acid metabolism, an essential process in generating inflammation in the body.
Leukotriene modifiers work through two distinct mechanisms:
Leukotriene modifiers work through two distinct mechanisms:
1.7K