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

Abstract

Seven new tanzawaic acid derivatives, steckwaic acids E-K (<b>1</b>-<b>7</b>), and one new benzene derivate (<b>8</b>), together with seven known tanzawaic acid analogues (<b>9</b>-<b>16</b>) were isolated from the marine algicolous fungus <i>Penicillium steckii</i> SCSIO 41040. The structures and absolute configurations of these new compounds (<b>1</b>-<b>8</b>) were determined by spectroscopic analyses, X-ray diffraction, and comparison of ECD spectra to calculations. Compounds <b>2</b>, <b>10</b>, and <b>15</b> inhibited lipopolysaccharide (LPS)-induced nuclear factor kappa-B (NF-κB) with IC₅₀ values of 10.4, 18.6, and 15.2 μM, respectively. Compound <b>2</b> 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.