New Sesquiterpenoids from the Mangrove-Derived Fungus Talaromyces sp. as Modulators of Nuclear Receptors

Four new sesquiterpenoids, talaroterpenes A-D ( - ), were isolated from the mangrove-derived fungus sp. SCSIO 41412. The structures of compounds - were elucidated through comprehensive NMR and MS spectroscopic analyses. The absolute configurations of - were assigned based on single-crystal X-ray diffraction and calculated electronic circular dichroism analysis. Talaroterpenes A-D ( - ) were evaluated with their regulatory activities on nuclear receptors in HepG2 cells. Under the concentrations of 200 μM, , and exhibited varying degrees of activation on and , while showed the strongest activities. Furthermore, induced significant alterations in the expression of downstream target genes and of RORα, and the in silico molecular docking analysis supported the direct binding interactions of with RORα protein. This study revealed that talaroterpene D ( ) was a new potential non-toxic modulator of nuclear receptors.