Peniditerpenoids A and B: two unprecedented indole diterpenoids with osteoclast differentiation inhibitory activity from the mangrove-sediment-derived fungus Penicillium sp.

An unprecedented diseco indole diterpenoid and a rare indole diterpenoid N-oxide derivative, named peniditerpenoids A (1) and B (2), along with three biosynthetically related known ones (3–5), were isolated from the mangrove sediment-derived fungus Penicillium sp. SCSIO 41411. Their structures were elucidated by detailed interpretation of NMR spectroscopic and mass spectrometric data. The absolute configurations were confirmed by NOESY experiments, ECD calculations, as well as X-ray single crystal diffraction analyses. The plausible biosynthetic pathways of those indole diterpenoids were described. Peniditerpenoids A (1) exhibited the inhibitory effect on lipopolysaccharide (LPS)-induced nuclear factor-κB (NF-κB) with IC50 value of 10.8 μM, and it also suppressed RANKL induced osteoclast differentiation in bone marrow macrophages cells (BMMCs). It is revealed that 1 with the unusual diseco indole diterpenoid moiety may have potential for the treatment of osteoclast-related diseases as a promising osteoclast differentiation inhibitor.