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

Abstract

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.

Natural Sesquiterpenoids, Diterpenoids, Sesterterpenoids, and Triterpenoids with Intriguing Structures from 2017 to 2022

“…Applanoids A—E ( 146 — 150 ) represent the first example of Ganoderma triterpenoids 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. [ 168 ] Among of them, 146 , 147 , and 148 could significantly activate human pregnane X receptor (hPXR), and molecular docking revealed that they were docked well into the ligand binding domain by the establishment of hydrogen bonds and van der Waals effects. [ 168 ] Irpexolidal ( 151 ), a triterpenoid with an unprecedented 6/5/6/5/6/5 fused polycyclic skeletal system carbon skeleton, has been isolated from the fruiting bodies of the medicinal fungus Irpex lacteus .…”

“…[ 168 ] Among of them, 146 , 147 , and 148 could significantly activate human pregnane X receptor (hPXR), and molecular docking revealed that they were docked well into the ligand binding domain by the establishment of hydrogen bonds and van der Waals effects. [ 168 ] Irpexolidal ( 151 ), a triterpenoid with an unprecedented 6/5/6/5/6/5 fused polycyclic skeletal system carbon skeleton, has been isolated from the fruiting bodies of the medicinal fungus Irpex lacteus . [ 169 ] The structure of 151 has been established by ECD calculation, and DP4 + probability based on GIAO NMR chemical shift calculations.…”

Natural Sesquiterpenoids, Diterpenoids, Sesterterpenoids, and Triterpenoids with Intriguing Structures from 2017 to 2022

“…[157] Applanoids A-E (146 -150 ) represent the first example ofGanoderma triterpenoids 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. [158] Among of them,146 , 147 , and 148 could significantly activate human pregnane X receptor (hPXR), and molecular docking revealed that they were docked well into the ligand binding domain by the establishment of hydrogen bonds and van der Waals effects. [158] Irpexolidal (151 ), a triterpenoid with an unprecedented 6/5/6/5/6/5 fused polycyclic skeletal system carbon skeleton, has been isolated from the fruiting bodies of the medicinal fungus Irpex lacteus .…”

“…[158] Among of them,146 , 147 , and 148 could significantly activate human pregnane X receptor (hPXR), and molecular docking revealed that they were docked well into the ligand binding domain by the establishment of hydrogen bonds and van der Waals effects. [158] Irpexolidal (151 ), a triterpenoid with an unprecedented 6/5/6/5/6/5 fused polycyclic skeletal system carbon skeleton, has been isolated from the fruiting bodies of the medicinal fungus Irpex lacteus . [159] The structure of 151 has been established by ECD calculation, and DP4 + probability based on GIAO NMR chemical shift calculations.…”

Novel A-seco-nortriterpenoids from Ganoderma cochlear inhibiting Tau pathology by activating AMPK-ULK1-mediated autophagy

“…Ganoderma has attracted significant attention from pharmacologists, chemists, and phytochemists because it has long been used as a traditional medicine in many countries 1,2 and is also an important source of meroterpenoids and lanostane triterpenoids with significant bioactivities and captivating structures. [3][4][5][6][7][8][9] In particular, Ganoderma triterpenoids (GTs) have been widely studied as the main active constituents of Ganoderma for their anti-tumor, anti-aging, liver-protective, and neuroprotective activities. Notably, previous studies have confirmed that GTs can reverse cognitive impairment, 10 attenuate LPS-induced inflammation and apoptosis, 11 promote amyloid-β clearance and inhibit Tau pathology through activating autophagy, 6,12 suggesting that GTs exhibit huge potential in the treatment of neurodegenerative diseases.…”