ent-Atisane Diterpenoids with Anti-Influenza Virus Activity from Mangrove Plant Excoecaria agallocha L

Three new ent-atisane diterpenoids, named agallolides N‒P (1-3) together with nine known diterpenoids (4-12) were isolated from the stems and twigs of the mangrove plant, Excoecaria agallocha L. . Various techniques, including high-resolution electrospray ionization mass spectrometry, spectroscopic methods, ¹³C-NMR calculations, DP4+ probability analysis, and equivalent circulating density calculations were applied to determine their molecular structures. The anti-influenza virus activities of 1-12 against A/PR/8/34 (H1N1), ZX1109 (H1N1, oseltamivir-resistant virus), HK68 (H3N2), and B/Florida/78/2015 were evaluated. Compounds 8 and 12 showed significant antiviral activities against those four virus strains with EC₅₀ values ranging from 0.54 to 19.53 µM. Moreover, compound 8 exhibited notable antiviral activity against A/PR/8/34, ZX1109, and B/Florida/78/2015 with EC₅₀ values of 2.82, 3.45, and 0.54 µM, respectively, which were more potent than the positive control oseltamivir. These findings suggest that compound 8 may be a potential structure basis for developing anti-influenza agents.