Deng Lihua, Song Chengcheng, Niu Youhong, Li Qin, Wang Meng, Wu Yan-Fen, Ye Xin-Shan
State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University Xue Yuan Road No. 38 Beijing 100191 China
Engineering Research Center of Glycoconjugates, Ministry of Education, Jilin Provincial Key Laboratory of Chemistry and Biology of Changbai Mountain Natural Drugs, School of Life Sciences, Northeast Normal University Changchun 130024 China.
RSC Med Chem. 2021 Aug 24;12(11):1968-1976. doi: 10.1039/d1md00210d. eCollection 2021 Nov 17.
Bergenin, which is isolated from species, exhibits various pharmacological properties. In the search for new types of immunosuppressants, a series of bergenin derivatives were designed and synthesized, and their immunosuppressive effects were evaluated by the CCK-8 assay. The experimental data demonstrated that compounds and showed the strongest inhibition effects on mouse splenocyte proliferation (IC = 3.52 and 5.39 μM, respectively). Further studies revealed that the inhibitory effect may come from the suppression of both IFN-γ and IL-4 cytokines. Alkylated derivatives of bergenin with -hexyl and -heptyl on the two phenolic hydroxyl groups showed better inhibitory activities. The hydrophobicity of bergenin derivatives, the configuration of the 4-OH in bergenin, and the ability to form hydrogen bonds of the substituents on the -4 position are important to the immunosuppressive activity. This work proved that the modifications of bergenin may represent a new route to the discovery of a new class of immunosuppressive agents.
岩白菜素是从[具体物种]中分离得到的，具有多种药理特性。在寻找新型免疫抑制剂的过程中，设计并合成了一系列岩白菜素衍生物，并通过CCK - 8法评估了它们的免疫抑制作用。实验数据表明，化合物[具体化合物]和[具体化合物]对小鼠脾细胞增殖表现出最强的抑制作用（IC分别为3.52和5.39 μM）。进一步研究表明，这种抑制作用可能源于对IFN - γ和IL - 4细胞因子的抑制。在两个酚羟基上带有 - 己基和 - 庚基的岩白菜素烷基化衍生物表现出更好的抑制活性。岩白菜素衍生物的疏水性、岩白菜素中4 - OH的构型以及 - 4位取代基形成氢键的能力对免疫抑制活性很重要。这项工作证明，岩白菜素的修饰可能代表了发现一类新型免疫抑制剂的新途径。
