Structural diversity and biological activities of indole-diterpenoids from Penicillium janthinellum by co-culture with Paecilomyces formosus

[Display omitted] •Structural diversity of indole-diterpenoids from two co-cultured fungi was described.•These indole-diterpenoids displayed extensive biological activities.•The anti-influenza mechanism of compounds 1, 2, and 7 was further investigated.•The SAR of PTPs inhibitory activity of 1, 2, 4, 5, 9–16, and 19–21 was summarized. Co-culturing the marine-derived fungi Penicillium janthinellium with Paecilomyces formosus led to the isolation of nine new indole-diterpenes, janthinellumines A–I (1–9), along with twelve known analogues (10–21). The chemical structures including their absolute configurations of them were assigned by the analysis of extensive spectroscopic data and calculated ECD and VCD methods. These indole-diterpenoids displayed extensive biological activities, including anti-influenza A virus, protein tyrosine phosphatase (PTP) inhibitory, and anti-Vibrio activities. Among them, the anti-influenza mechanism of compounds 1, 2, and 7 was further investigated using neuraminidase inhibitory assay, molecular docking, and reverse genetics methods, suggesting that 1, 2, and 7 could interact with Arg371 of the viral neuraminidase. The structure–activity relationship (SAR) of PTPs inhibitory activity for indole-diterpene derivatives (1, 2, 4, 5, 9–16, and 19–21) was also summarized.