Congested heptacyclic meroterpenoids with anti-SARS-CoV-2 and anti-inflammatory activities from mangrove endophytic fungus Talaromyces amestolkiae SCNU–F0041

Abstract

Under the guidance of LC‒MS/MS-based molecular networking, three previously undescribed berkeleyacetal type meroterpenoids, amestolknoids A-C (1–3), together with ten known analogues (4–13) were isolated and identified from the mangrove endophytic fungus Talaromyces amestolkiae SCNU–F0041. Amestolknoids A (1) and B (2) are unprecedentedly congested 6/7/6/5/5/5/5 heptacyclic scaffolds characterized by two chiral spiroketal centers. Amestolknoids A (1) and C (3) represent the first examples of chlorinated berkeleyacetal type meroterpenoids. Their structures were established by extensive spectroscopic analyses and single crystal X-ray diffraction. Bioassays revealed that amestolknoid C (3) exhibited excellent antiviral activity against SARS-CoV-2 with an EC₅₀ value of 2.50 μM and strong inhibitory effects on nitric oxide production in lipopolysaccharide-activated RAW 264.7 cells with an IC₅₀ value of 4.10 μM. Compounds 2, 4, 6, 9 and 11 showed moderate to good anti-inflammatory activities with IC₅₀ values of 41.78, 3.91, 43.52, 20.79, and 33.26 μM, respectively.