Department of Pharmacognosy and Utilization Key Laboratory of Northeast Plant Materials, School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang 110016, China.
J Org Chem. 2021 Aug 20;86(16):11220-11236. doi: 10.1021/acs.joc.1c00812. Epub 2021 Jul 21.
Silverweed cinquefoil roots, as dietary supplements, foods, and medicines, are widely used in western areas of China, specifically in Tibet Autonomous Region and Gansu and Qinghai Provinces. In this paper, 10 new natural pentacyclic triterpenoid saponins (-), named poterinasides A-J, along with 14 known compounds (-) were isolated and purified from silverweed cinquefoil roots. The chemical structures of - were established by extensive analysis of 1D and 2D NMR data and mass spectrometric data. Poterinasides A (), B (), and G () with the unique position of substituents on the E ring had never been discovered in natural products before. Saponins -, , and displayed potent hepatoprotective activities, and -, , , , , , and - showed outstanding anti-inflammatory effects. On the basis of the present results, some structure-activity relationships were summarized, in which 3α-OH, 19β-CH, 20α-CH, 20β-CH, 21α-OH, and 30-OH groups in isolated pentacyclic triterpenoid saponins were found to strengthen the hepatoprotective and anti-inflammatory activities, respectively. Further, the following pharmacophore-based virtual screening and docking studies on special targets proteins, SIRT1 and COX-2, revealed roughly similar results with the structure-activity relationships, and this combination method was used for the first time for active natural compound screening.
翻白草根作为膳食补充剂、食品和药物，在中国西部地区（尤其是西藏自治区和甘肃、青海两省）广泛应用。本文从翻白草根中分离并纯化得到了 10 种新的天然五环三萜皂苷（-），命名为 poterinaside A-J，以及 14 种已知化合物（-）。通过对 1D 和 2D NMR 数据和质谱数据的广泛分析，确定了 - 的化学结构。Poterinaside A ()、B () 和 G () 具有 E 环取代基的独特位置，以前从未在天然产物中发现过。皂苷 -、- 和 - 具有很强的保肝活性，-、-、-、-、-、-、- 和 - 具有很强的抗炎作用。基于目前的结果，总结了一些构效关系，其中分离得到的五环三萜皂苷中的 3α-OH、19β-CH、20α-CH、20β-CH、21α-OH 和 30-OH 基团被发现分别增强了保肝和抗炎活性。此外，基于药效团的虚拟筛选和对特殊靶点蛋白 SIRT1 和 COX-2 的对接研究表明，与构效关系大致相似，这种组合方法首次用于活性天然化合物的筛选。
