Anti-inflammatory acetylenic meroterpenoids from the ascidian-derived fungus Amphichorda felina SYSU-MS7908

Abstract

A combination strategy of 13C NMR and bioinformatics was established to expedite the discovery of acetylenic meroterpenoids from the ascidian-derived fungus Amphichorda felina SYSU-MS7908. This approach led to the identification of 13 acetylenic meroterpenoids (1–13) and four biogenic analogs (14–17), including five new ones named felinoids A-E (1–4 and 15). Their structures and absolute configurations were elucidated using extensive spectroscopy, ECD quantum chemical calculations, and single-crystal X-ray diffraction analysis. Compound 1 possessed a rare cyclic carbonate in natural acetylenic meroterpenoids. The plausible shikimate-terpenoid biosynthetic pathways of 1–4 were also postulated. Five of these isolates exhibited anti-inflammatory activity by inhibiting NO production in LPS-induced RAW264.7 cells (IC50 = 11.6–19.5 μM). Moreover, oxirapentyn E diacetate showed a dose-dependent inhibition of pro-inflammatory cytokines IL-6 and TNF-α. Structural modification of oxirapentyn B yielded 29 new derivatives, among which seven showed improved activity (IC50 < 3 μM) and higher selectivity index (SI > 22). The structure–activity relationship study indicated that 7, 8-epoxy, and 6-acylation were crucial for the activity. These findings may provide a powerful tool to accelerate the discovery of new fungal acetylenic meroterpenoids for future anti-inflammatory drug development.