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

A chemical investigation on the marine-derived fungus Penicillium crustosum SCNU-F0046 resulted in the isolation and characterization of four new benzofurans (1, 2, 5, 6) and four known analogues (3, 4, 7, 8). 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 1 exhibited moderate antibacterial activity, while compound 6 showed antifungal activity. In addition, the anti-inflammatory activity of aza-benzofuran compounds (1-4) was also evaluated. Bioassays revealed that compounds 1 and 4 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 1 and 4 exhibited an ideal fit within the active site of the murine inducible nitric oxide synthase (iNOS), establishing characteristic hydrogen bonds.