Phomazaphilonoids A and B, Anti-inflammatory Polyketides from the Fungus <i>Phomopsis</i> sp. SCNU-F0049

Phomazaphilones A and B (<b>1</b> and <b>2</b>), azaphilones possessing a 5/6/6-fused tricyclic ring system, along with two known analogues, were discovered from the fungus <i>Phomopsis</i> sp. SCNU-F0049 was collected from the mangrove sediment. The structures were elucidated by extensive spectroscopic data and single-crystal X-ray diffraction. Phomazaphilone A (<b>1</b>) possesses a new 6,7,8,8<i>a</i>-tetrahydro-2<i>H</i>-furo[4,3,2-de]isoquinolin-2-one core, and phomazaphilone B (<b>2</b>) possesses a new 6,7,8,8<i>a</i>-tetrahydro-2<i>H</i>,5<i>H</i>-furo[4,3,2-de]isochromene-2,5-dione heterocyclic core. A possible biosynthetic pathway was proposed based on genome sequence analysis. Phomazaphilone B (<b>2</b>) inhibited NO production in LPS-stimulated RAW264.7 cells with an IC₅₀ value of 3.28 ± 0.24 μM and suppressed the expression levels of proinflammatory cytokines TNF-α and IL-6 in a dose-dependent manner without cytotoxicity.