Suppression of RANKL-Induced Osteoclastogenesis by the Metabolites from the Marine Fungus Aspergillus flocculosus Isolated from a Sponge Stylissa sp.

A new α-pyrone merosesquiterpenoid possessing an angular tetracyclic carbon skeleton, ochraceopone F ( 1 ), and four known secondary metabolites, aspertetranone D ( 2 ), cycloechinulin ( 3 ), wasabidienone E ( 4 ), and mactanamide ( 5 ), were isolated from the marine fungus Aspergillus flocculosus derived from a sponge Stylissa sp. collected in Vietnam. The structures of Compounds 1 - 5 were elucidated by analysis of 1D and 2D NMR spectra and MS data. All the isolated compounds were evaluated for anti-proliferation activity and their suppression effects on receptor activator of nuclear factor κB ligand (RANKL)-induced osteoclast differentiation using tartate-resisant acid phosphatase (TRAP). Compounds 1 - 5 had no anti-proliferative effect on human cancer cell lines up to 30 μg/mL. Among these compounds, aspertetranone D ( 2 ) and wasabidienone E ( 4 ) exhibited weak osteoclast differentiation inhibitory activity at 10 μg/mL. However, mactanamide ( 5 ) showed a potent suppression effect of osteoclast differentiation without any evidence of cytotoxicity.