Benzofuran Derivatives with Antimicrobial and Anti-Inflammatory Activities from Penicillium crustosum SCNU-F0046

A chemical investigation on the marine-derived fungus <i>Penicillium crustosum</i> SCNU-F0046 resulted in the isolation and characterization of four new benzofurans (<b>1</b>, <b>2</b>, <b>5</b>, <b>6</b>) and four known analogues (<b>3</b>, <b>4</b>, <b>7</b>, <b>8</b>). Their structures were elucidated by a combination of mass, NMR spectroscopy, electronic circular dichroism (ECD) calculations and X-ray crystallographic analyses. The antimicrobial experiments disclosed compound <b>1</b> exhibited moderate antibacterial activity, while compound <b>6</b> showed antifungal activity. In addition, the anti-inflammatory activity of aza-benzofuran compounds (<b>1</b>-<b>4</b>) was also evaluated. Bioassays revealed that compounds <b>1</b> and <b>4</b> exhibited anti-inflammatory activity by inhibiting nitric oxide release without cytotoxicity in lipopolysaccharide (LPS)-stimulated RAW 264.7 mouse macrophages with IC₅₀ values of 17.3 and 16.5 μM, respectively. The docking study revealed that compounds <b>1</b> and <b>4</b> exhibited an ideal fit within the active site of the murine inducible nitric oxide synthase (iNOS), establishing characteristic hydrogen bonds.