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

Abstract

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