Tanzawaic Acid Derivatives from the Marine-Derived Penicillium steckii as Inhibitors of RANKL-Induced Osteoclastogenesis

Seven new tanzawaic acid derivatives, steckwaic acids E–K (1–7), and one new benzene derivate (8), together with seven known tanzawaic acid analogues (9–16) were isolated from the marine algicolous fungus Penicillium steckii SCSIO 41040. The structures and absolute configurations of these new compounds (1–8) were determined by spectroscopic analyses, X-ray diffraction, and comparison of ECD spectra to calculations. Compounds 2, 10, and 15 inhibited lipopolysaccharide (LPS)-induced nuclear factor kappa-B (NF-κB) with IC50 values of 10.4, 18.6, and 15.2 μM, respectively. Compound 2 could suppress the receptor activator of NF-κB ligand (RANKL)-induced osteoclast differentiation in bone marrow macrophage cells (BMMCs). To the best of our knowledge, this is the first report of osteoclastogenesis inhibitory activity for tanzawaic acid derivatives.