A New α-Cyclopiazonic Acid Alkaloid Identified from the Weizhou Island Coral-Derived Fungus Aspergillus flavus GXIMD 02503

A new oxygenated tricyclic cyclopiazonic acid (CPA) alkaloid, asperorydine Q (1), along with seven known compounds, namely, asperorydines O (2) and J (3), speradine H (4), cyclopiamides A (5) and H (6), saadamysin (7), and pyrazinemethanol (8), were isolated from the coral-associated Aspergillus flavus GXIMD 02503. The structures were elucidated by physicochemical properties and comprehensive spectroscopic data analysis. Compounds 1-5 and 7-8 exhibited potent inhibition of lipopolysaccharide (LPS)-induced nuclear factor-κB (NF-κB) with the IC₅₀ values ranging from 6.5 to 21.8 μmol L⁻¹. In addition, the most potent one, pyrazinemethanol (8), dose-dependently suppressed receptor activator of NF-κB ligand (RANKL)-induced osteoclast differentiation without obvious cytotoxicity in bone marrow macrophages cells (BMMCs), suggesting it is a promising lead compound for the treatment of osteolytic diseases.