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

Phomazaphilones A and B (1 and 2), azaphilones possessing a 5/6/6-fused tricyclic ring system, along with two known analogues, were discovered from the fungus Phomopsis 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 (1) possesses a new 6,7,8,8a-tetrahydro-2H-furo[4,3,2-de]isoquinolin-2-one core, and phomazaphilone B (2) possesses a new 6,7,8,8a-tetrahydro-2H,5H-furo[4,3,2-de]isochromene-2,5-dione heterocyclic core. A possible biosynthetic pathway was proposed based on genome sequence analysis. Phomazaphilone B (2) 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.