Maydistacins A–G, Terpestacin-type Sesterterpenoids with Anti-inflammatory Activity from the Phytopathogenic Fungus Bipolaris maydis

Seven undescribed terpestacin-type sesterterpenoids, maydistacins A–G (1–7), along with two known congeners (8 and 9), were isolated from the phytopathogenic fungus Bipolaris maydis collected from the leaves of Hypericum longistylum. The structures of 1–7 were elucidated based on extensive spectroscopic analysis, chemical methods, NMR calculations with DP4+ probability analysis, and comparison of experimental and calculated electronic circular dichroism (ECD) calculations. In vitro anti-inflammatory effects of these compounds were tested in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages. Compound 1 exhibited inhibition of the production of nitric oxide in LPS-induced macrophages, with an IC50 value of 19 ± 2 μM. A dexamethasone control displayed an IC50 value of 6.7 ± 0.6 μM. Compound 1 is the first terpestacin-type sesterterpenoid reported to display anti-inflammatory activity and may provide a novel chemical scaffold for the discovery of new anti-inflammatory drugs.