Key Laboratory of Chemical Biology of Ministry of Education, School of Pharmaceutical Sciences, Shandong University, Jinan 250012, PR China.
National Glycoengineering Research Center, Shandong University, Jinan 250012, PR China.
Bioorg Med Chem. 2021 Jan 1;29:115854. doi: 10.1016/j.bmc.2020.115854. Epub 2020 Nov 13.
Kinsenoside is the major bioactive component from herbal medicine with a broad range of pharmacological functions. Goodyeroside A, an epimer of kinsenoside, remains less explored. In this report we chemically synthesized kinsenoside, goodyeroside A and their analogues with glycan variation, chirality inversion at chiral center(s), and bioisosteric replacement of lactone with lactam. Among these compounds, goodyeroside A and its mannosyl counterpart demonstrated superior anti-inflammatory efficacy. Furthermore, goodyeroside A was found to suppresses inflammatory through inhibiting NF-κB signal pathway, effectively. Structure-activity relationship is also explored for further development of more promising kinsenoside analogues as drug candidates.
金雀异皂苷是一种具有广泛药理功能的草药中的主要生物活性成分。金雀异糖苷 A 是金雀异皂苷的差向异构体，其研究较少。在本报告中，我们化学合成了金雀异皂苷、金雀异糖苷 A 及其具有糖基变化、手性中心手性反转和内酯酰胺生物等排体取代的类似物。在这些化合物中，金雀异糖苷 A 及其甘露糖苷类似物表现出优异的抗炎效果。此外，还发现金雀异糖苷 A 通过抑制 NF-κB 信号通路有效抑制炎症。还探讨了构效关系，以进一步开发更有前途的金雀异皂苷类似物作为药物候选物。
