New metabolites including an uncommon 3/5/6/6/11/6/6 fused-ring skeleton meroterpenoid from Penicillium brefeldianum SMU03 and their antifibrotic activities

Penicine A (1), a meroterpenoid with novel 3/5/6/6/11/6/6 polycyclic backbone, along with two new metabolites, penicines B (2) and C (4), and six known compounds, were isolated from the mangrove rhizosphere soil-derived fungus Penicillium brefeldianum SMU03. Their structures were elucidated by spectroscopic and quantum chemical computational methods. Notably, 1 possesses an uncommon dioxatricyclo3.3.1.0^2,4nonane scaffold, a dioxaspiro4.5decane motif and an unusual bridgehead double bond (anti-Bredt system). A plausible biosynthetic pathway, involving tandem intermolecular 4 + 2 cycloaddition reactions, is postulated. Finally, meroterpenoids 1 and 3 exhibit potent antifibrotic activity in TGF-β1-induced human renal proximal tubular epithelial cells.