Discovery of Polyketides and Alkaloids From the Mangrove Endophytic Fungus <i>Diaporthe</i> sp. and Their Anti‐Osteoclastogenic Bioactivities

Two new compounds, 5-methoxymethylmellein (1) and 6-benzyl-2-hydroxy-5-methoxy-3-methylpyradine (2), along with nine known compounds (3-11), were obtained from the mangrove endophytic fungus Diaporthe sp. SCSIO 41011. Their structures were determined based on extensive spectroscopic analysis and by comparison with literature. The absolute configuration of 1 was assigned by electronic circular dichroism calculations. The structure of naturally rare compound 2 was unambiguously confirmed by single-crystal X-ray diffraction analysis. Notably, compound 4 displayed inhibition of lipopolysaccharide-induced nuclear factor kappa B in RAW264.7 macrophages at 20 µM. It further dose-dependently suppressed receptor activator of nuclear factor-κB ligand-induced osteoclast differentiation in bone marrow macrophage cells with an EC₅₀ value of 19.0 µM, without observed cytotoxicity. Our findings provided 4 as a promising lead compound for the treatment of osteolytic diseases.