Secondary Metabolites from the Endophytic Fungus Letendraea helminthicola A820 with Anti-inflammatory Activity

Two undescribed letendrones A-B (1-2), along with three known compounds, ZL-6 (3), dankasterone B (4), and minimoidione B (5) were isolated from the Aquilaria-derived fungus Letendraea helminthicola A820. The structures of 1 and 2 were established by analysis of spectroscopes including 1D/2D NMR, IR, UV, and HRESIMS. Among them, the configuration of 1 was further confirmed by single-crystal X-ray diffraction. Letendrones A and B were the new phenalenyl derivatives with radical form that were firstly found in nature. In addition, bioactivity of these compounds was evaluated and compounds 3-5 exhibited inhibitory activity against LPS-induced NO production in macrophages with IC₅₀ values of 4.64, 13.90, and 34.07 μM. Furthermore, potential targets of the new compounds were analyzed by molecular docking in silico. As a result, compound 1 showed high binding with predicted 5-HT_2c receptor (▵G=-8.2 kcal/mol) potentially associated with depression disease, and compound 2 showed significant connection with phosphodiesterase 3 A (▵G=-9.4 kcal/mol) probably against cardiovascular disorders. Our findings firstly reported the high symmetry phenalenyl compounds from natural products which would provide a basis for further development and utilization of the secondary metabolites from the endophytic fungus Letendraea helminthicola A820.