Applanoids A-E as the First Examples of C-15/C-20 Michael Adducts in Ganoderma Triterpenoids and Their PXR Agonistic Activity

Comprehensive Summary Ganoderma triterpenoids (GTs), a class of major active constituents of Ganoderma fungi, possess diverse structures and remarkable activities. In the present study, nine new GTs, namely applanoids A-I (1-9), were isolated from the medicinal fungus of Ganoderma applanatum. Their structures including absolute configurations were established by comprehensive spectroscopic analyses and ECD calculation. Applanoids A-E (1-5) represent the first example of GTs with 6/6/5/6/5 pentacyclic system and the formation of the ether ring between C-15 and C-20 involves Michael addition reaction. Furthermore, compounds 1-8 were evaluated for their human pregnane X receptor (hPXR) agonistic activity using dual-luciferase reporter gene assay, and the results showed that compounds 1, 2 and 4 can dose-dependently activate hPXR. This investigation further illustrated the structural diversity of GTs and provided new insights for searching PXR agonists from GTs.

Automated summary

In this study, nine new Ganoderma triterpenoids (GTs) were isolated from the medicinal fungus Ganoderma applanatum, and their structures and absolute configurations were determined. Compounds 1-8 were evaluated for their hPXR agonistic activity, and compounds 1, 2, and 4 showed dose-dependent activation of hPXR. This study further expands our knowledge of the structural diversity of GTs and provides insights for the discovery of PXR agonists from GTs.