Neuroprotective azaphilones from a deep-sea derived fungus sp. SCSIO41030.

Ten azaphilones including one pair of new epimers and three new ones, penineulones A-E (1-5) with the same structural core of angular deflectin, were obtained from a deep-sea derived sp. SCSIO41030 fermented on a liquid medium. Their structures including absolute configurations were elucidated using chiral-phase HPLC analysis, extensive NMR spectroscopic and HRESIMS data, ECD and NMR calculations, and by comparing NMR data with literature data. Biological assays showed that the azaphilones possessed no antitumor and anti-viral (HSV-1/2) activities at concentrations of 5.0 μM and 20 μM, respectively. In addition, azaphilones 8 and 9 showed neuroprotective effects against Aβ-induced neurotoxicity in primary cultured cortical neurons at a concentration of 10 μM. Azaphilones 8 and 9 dramatically promoted axonal regrowth against Aβ-induced axonal atrophy. Our study indicated that azaphilones could be promising lead compounds for neuroprotection.