Biscaesalmins A and B from Caesalpinia minax, highly oxidized dimeric cassane diterpenoids as interleukin-1β inhibitors

• 作者: Yunshao Xu Tian Zhang Lu Feng Zheling Feng Qingwen Zhang Yang Ye Lishe Gan Ligen Lin
• 来源期刊: 中国化学快报（英文版）
• 年，卷（期）: 2021,（4）
• 所属期刊栏目: Communications
• 页码范围: 1475-1479
• 页数: 5页
• 语种: 英文

摘要

To search naturally occurring interleukin-1β (IL-1β) inhibitors, biscaesalmins A (1) and B (2), two highly oxidized dimeric cassane diterpenoids with a newly formed alicyclic skeleton, have been isolated from the traditional Chinese medicine Kushilian (Caesalpinia minax). Their full structures were determined by comprehensive spectroscopic analysis and quantum chemical TD-DFT (time-dependent density functional theory) calculation. Biosynthetically, 1 and 2 were formed via an intermolecular [4+2] Diels-Alder cycloaddition of two monomers, affording an additional six-membered carbon ring linkage. Compounds 1 and 2 inhibited nitric oxide production on lipopolysaccharide-stimulated THP-1 macrophages, with IC50 values being at 1.20 ± 0.23 and 2.30 ± 0.15 μmol/L, respectively. Furthermore, compound 1 inhibited NLRP3 (NOD-, LRR- and pyrin domain-containing protein 3) inflammasome-mediated IL-1β production and blocked the migration of macrophages towards adipocyte conditioned medium. Biscaesalmins A and B might be candidates for treating inflammation-related metabolic diseases.