Inhibitory effect of triterpenoids from the mushroom Inonotus obliquus against α-glucosidase and their interaction: Inhibition kinetics and molecular stimulations
Inhibitory effect of triterpenoids from the mushroom Inonotus obliquus against α-glucosidase and their interaction: Inhibition kinetics and molecular stimulations
复制标题
桦褐孔菌三萜类化合物对 α-葡萄糖苷酶的抑制作用及其相互作用：抑制动力学和分子刺激
DOI：
10.1016/j.bioorg.2021.105276
复制
发表时间：
2021-08-24
影响因子：
5.1
通讯作者：
Wu, Qing-Ping
中科院分区：
文献类型：
--
作者：
Chen, Shao-Dan;Yong, Tian-Qiao;Wu, Qing-Ping
从蘑菇桦褐孔菌中分离得到一系列三萜化合物(1-46)，其中包括12个新化合物(1-12)。所有化合物的结构均经波谱分析确定，并与文献数据进行比较。三萜1-3、6、7、16、24、25、27、38、43、44和46对α-葡萄糖苷酶有较强的抑制作用，其IC50值在11.5~81.8微米之间，并讨论了它们的构效关系。Inonotusol F(24)的抑制活性最强，对α-葡萄糖苷酶呈非竞争性抑制。分子对接和分子动力学模拟进一步证明GLU302和PHE298是吲哚青霉素F(24)抑制α-葡萄糖苷酶的关键氨基酸。本研究揭示了三萜类化合物在解释桦褐孔菌降血糖作用中的重要作用，为进一步开发利用桦褐孔菌提供了重要依据。
Bioassay-guided fractionation led to the isolation of a series of triterpenoids (1-46) including 12 new ones (1-12) from the mushroom Inonotus obliquus. The structures of all the compounds were elucidated by spectroscopic analysis as well as by comparison with literature data. Triterpenoids 1-3, 6, 7, 16, 24, 25, 27, 38, 43, 44 and 46 showed strong alpha-glucosidase inhibition, with IC50 values from 11.5 to 81.8 mu M. Their structure-activity relationships were discussed. Inonotusol F (24) showed the strongest inhibitory activity and it presented noncompetitive inhibition against alpha-glucosidase. Molecular docking and molecular dynamics stimulation further demonstrated that GLU302 and PHE298 were key amino acids for the inhibition of inonotusol F (24) towards alpha-glucosidase. This study indicates the vital role of triterpenoids in explaining hypoglycemic effect of Inonotus obliquus and provides important evidence for further development and utilization of this mushroom.