New meroterpenoids featuring a rare 3/5/6/6/11/6/6 fused-ring skeleton from Penicillium brefeldianum SMU03 and their antifibrotic activities

Penicine A (1), a meroterpenoid featuring a novel 3/5/6/6/11/6/6 polycyclic backbone, together 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. The structures of these metabolites were elucidated through extensive spectroscopic analysis combined with quantum chemical calculations. Notably, 1 exhibits a highly unusual molecular architecture, incorporating a dioxaspiro4.5decane motif and a rare bridgehead double bond (anti-Bredt system). A plausible biosynthetic pathway, involving sequential intermolecular 4 + 2 cycloaddition reactions, is proposed. Additionally, meroterpenoids 1 and 3 demonstrate significant antifibrotic activity in transforming growth factor β1 (TGF-β1)-induced human renal proximal tubular epithelial cells.