Cytochalasins from the marine-derived fungus Acremonium implicatum DFFSCS001 and their anti-inflammatory activities

Nine undescribed cytochalasins, acrechalasins A‒I, together with three known analogs 21-O-deacetyl-L-696,474 and diaporthichalasins B and A were isolated from the marine-derived fungus Acremonium implicatum DFFSCS001. Their structures were elucidated by spectroscopic methods, and the absolute configurations of acrechalasins C and D and diaporthichalasin B were determined by single-crystal X-ray diffractions. Among them, acrechalasins A and B had a rare open-chain cytochalasin skeleton with a monocyclic butyrolactam group. Biologically, acrechalasins A‒I and 21-O-deacetyl-L-696,474 exhibited significant inhibitory activity against lipopolysaccharide-induced nitric oxide production in RAW 264.7 cells with IC₅₀ values ranging from 1.30 to 20.31 μM. Their structure-bioactivity relationship was also discussed. Especially, acrechalasins A and D also significantly suppressed the protein expression of iNOS at the concentration of 10 μM. This is the first report on the anti-inflammatory activities of open-chain cytochalasins featuring a monocyclic butyrolactam group.