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.

A novel 1(2), 2(18)-di seco 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 EC 50 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. [ABSTRACT FROM AUTHOR]