Cuparene-type sesquiterpenes with neuroprotective activities from the edible mushroom Flammulina filiformis

Four new cuparene-type sesquiterpenes, flammuterpenols A − D (1–4), along with one known congener (5) were isolated from the solid culture of edible mushroom Flammulina filiformis. Their structures with a benzoxabicyclo[3.2.1]octane core were elucidated by integrated multiple spectroscopic techniques, electronic circular dichroism, and single crystal X-ray diffraction analysis. Biologically, compounds 1–5 were evaluated in vitro for their neuroprotective effects against 6-hydroxydopamine induced cell death in human neuroblastoma SH-SY5Y cells. All of them exhibited remarkable neuroprotective effects possessing the EC₅₀ values ranging from 0.93 ± 0.02 to 10.28 ± 0.10 μM. These findings not only enrich the structural diversity of cuparene-type sesquiterpenes, but also provide potential candidates for the further development of the neuroprotective agents.