Bioactive Pyridone Alkaloids from a Deep-Sea-Derived Fungus Arthrinium sp UJNMF0008

Eight new 4-hydroxy-2-pyridone alkaloids arthpyrones D-K (1-8), along with two known analogues apiosporamide (9) and arthpyrone B (10), were isolated from a deep-sea-derived fungus Arthrinium sp. UJNMF0008. The structures of the isolated compounds were elucidated on the basis of spectroscopic methods with that of 1 being established by chemical transformation and X-ray diffraction analysis. Compounds 1 and 2 bore an ester functionality linking the pyridone and decalin moieties first reported in this class of metabolites, while 3 and 4 incorporated a rare natural hexa- or tetrahydrobenzofuro[3,2-c]pyridin-3(2H)-one motif. Compounds 3-6 and 9 exhibited moderate to significant antibacterial activity against Mycobacterium smegmatis and Staphylococcus aureus with IC50 values ranging from 1.66-42.8 M, while 9 displayed cytotoxicity against two human osteosarcoma cell lines (U2OS and MG63) with IC50 values of 19.3 and 11.7 M, respectively.