Filicinic Acid-Based Meroterpenoids with Antiproliferative Activity against Prostate Cancer PC-3 Cells from Dryopteris wallichiana

Nine new structurally diverse filicinic acid–based meroterpenoids (1–9) with four kinds of carbon skeletons were isolated from the rhizomes of Dryopteris wallichiana. Their structures, including the absolute configurations, were elucidated by comprehensive analysis of spectroscopic data, quantum chemical calculations, and single-crystal X-ray diffraction. Structurally, compounds 1–4 feature an unprecedented 6/6/5/6/6/6 hexacyclic system with a rare oxaspiro[4.5]decane core linking the filicinic acid and ent-kaurane-type diterpene moieties. Compounds 5–6 are rare hybrids of filicinic acid and carotane-type sesquiterpene. Compound 7 is an unusual rearranged filicinic acid-carotane-type sesquiterpene meroterpenoid. Compounds 8–9 are two enantiomeric pairs of new meroterpenoids constructed by filicinic acid and a germarane-type sesquiterpene. A plausible biosynthetic pathway for the nine compounds was proposed. Notably, compounds 5, 6, (+)/(−)-8, and (+)/(−)-9 were discovered to possess antiproliferative activity against PC-3 cells based on virtual screening, and in vitro bioassay. An interactive preprint version of the article can be found at https://www.authorea.com/doi/full/10.22541/au.172666991.17272585/v1.