Drechmerin H, a novel 1(2), 2(18)-diseco indole diterpenoid from the fungus Drechmeria sp. as a natural agonist of human pregnane X receptor

Bioorg Chem. 2018 Sep:79:250-256. doi: 10.1016/j.bioorg.2018.05.001. Epub 2018 May 9.

Abstract

A novel 1(2), 2(18)-diseco indole diterpenoid, drechmerin H (1), was isolated from the fermentation broth of Drechmeria sp. together with a new indole diterpenoid, 2'-epi terpendole A (3), and a known analogue, terpendole A (2). Their structures were determined by HRESIMS, 1D and 2D NMR, ECD, and X-ray single crystal diffraction analyses as well as quantum chemical calculation. The abosulte configuration of terpendole A (2) was determined for the first time. Compound 1 displayed the significant agonistic effect on pregnane X receptor (PXR) with EC50 value of 134.91 ± 2.01 nM, and its interaction with PXR was investigated by molecular docking. Meantime, a plausible biosynthetic pathway for compounds 1-3 is also discussed in the present work.

Keywords: Agonistic effect; Drechmeria sp.; Indole diterpenoid; Molecular docking; Pregnane X receptor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biological Products / chemistry
  • Biological Products / isolation & purification
  • Biological Products / pharmacology*
  • Diterpenes / chemistry
  • Diterpenes / isolation & purification
  • Diterpenes / pharmacology*
  • Dose-Response Relationship, Drug
  • Hep G2 Cells
  • Humans
  • Hypocreales / chemistry*
  • Indoles / chemistry
  • Indoles / isolation & purification
  • Indoles / pharmacology*
  • Molecular Structure
  • Pregnane X Receptor / agonists*
  • Structure-Activity Relationship

Substances

  • Biological Products
  • Diterpenes
  • Indoles
  • NR1I2 protein, human
  • Pregnane X Receptor