Peniditerpenoids A and B: Oxidized Indole Diterpenoids with Osteoclast Differentiation Inhibitory Activity from a Mangrove-Sediment-Derived sp.

An unprecedented di--indole diterpenoid, peniditerpenoid A (), and a rare -oxide-containing indole diterpenoid derivative, peniditerpenoid B (), together with three known ones (-), were obtained from the mangrove-sediment-derived fungus sp. SCSIO 41411. Their structures were determined by the analysis of spectroscopic data, quantum chemical calculations, and X-ray diffraction analyses. Peniditerpenoid A () inhibited lipopolysaccharide-induced NF-κB with an IC value of 11 μM and further effectively prevented RANKL-induced osteoclast differentiation in bone marrow macrophages. studies demonstrated that exerted significant inhibition of NF-κB activation in the classical pathway by preventing TAK1 activation, IκBα phosphorylation, and p65 translocation. Furthermore, effectively reduced the level of NFATc1 activation, resulting in the attenuation of osteoclast differentiation. Our findings suggest that holds promise as an inhibitor with significant potential for the treatment of diseases related to osteoporosis.