Inhibitors of RANKL-induced osteoclast differentiation from the Marine Fungus Aspergillus flocculosus Isolated from a Sponge Stylissa sp.

Abstract

Large numbers of novel secondary metabolites from the ocean have structural diversities and potent bioactivities. Many marine organisms, especially microorganisms, have been attracting significant attention from natural product chemists and biologists due to the potential of marine natural products as drugs during recent years. As part of our continuing efforts to discover bioactive natural products from sponge-derived microorganisms, various marine sponges were collected and investigated for the isolation and identification of microorganisms. During studies on the diversity of fungi, a marine fungal strain 01NT-1.1.5, Aspergillus flocculosus derived from a sponge Stylissa sp., was isolated through experimental tools for the isolation of microorganisms. The crude extract of the strain was purified further by a reversed-phase HPLC to yield one new compound, ochraceopone F (1), and four known compounds aspertetranone D (2), cycloechinulin (3), wasabidienone E (4), and mactanamide (5). The structures of the known compounds were identified by 1D and 2D NMR analysis and comparison with literature data. All compounds were tested for anti-proliferative activity on human cancer cell lines and RANKL-induced osteoclast differentiation inhibitory effect using a TRAP assay. Among compounds 1-5, mactanamide (5) showed potent RANKL-induced osteoclast differentiation inhibitory effect. biologists due to the potential of marine natural products as drugs during recent years. As part of our continuing efforts to discover bioactive natural products from sponge-derived microorganisms, various marine sponges were collected and investigated for the isolation and identification of microorganisms. During studies on the diversity of fungi, a marine fungal strain 01NT-1.1.5, Aspergillus flocculosus derived from a sponge Stylissa sp., was isolated through experimental tools for the isolation of microorganisms. The crude extract of the strain was purified further by a reversed-phase HPLC to yield one new compound, ochraceopone F (1), and four known compounds aspertetranone D (2), cycloechinulin (3), wasabidienone E (4), and mactanamide (5). The structures of the known compounds were identified by 1D and 2D NMR analysis and comparison with literature data. All compounds were tested for anti-proliferative activity on human cancer cell lines and RANKL-induced osteoclast differentiation inhibitory effect using a TRAP assay. Among compounds 1-5, mactanamide (5) showed potent RANKL-induced osteoclast differentiation inhibitory effect.