Bipolaricins A–I, Ophiobolin-Type Tetracyclic Sesterterpenes from a Phytopathogenic Bipolaris sp. Fungus

A preliminary phytochemical investigation on the EtOAc extracts of the fungus Bipolaris sp. TJ403-B1 resulted in the identification of 12 ophiobolin-type phytotoxins ( 1 – 12 ), including nine new ones, termed bipolaricins A–I ( 1 – 9 ). The structures of 1 – 9 were elucidated via spectroscopic data (including HRESIMS and 1D and 2D NMR) and single-crystal X-ray diffraction (Cu Kα) analyses. All of the isolated compounds were tested in terms of HMG-CoA reductase inhibitory, anti-inflammatory, and cytotoxic activities. Compound 10 showed HMG-CoA reductase inhibitory activity (IC 50 = 8.4 ± 0.4 μM), and 2, 3, and 10 – 12 showed significant inhibitory potency against lipopolysaccharide (LPS)-induced nitric oxide production, with IC 50 values in the range of 5.1 ± 0.3 to 20 ± 1 μM. Further experiments showed that 10 could significantly inhibit the production of IL-1β, RANTES, MIP-1β, and TNF-α as well as enhance the release of IL-13 in macrophages through the inhibition of HO-1 induction as well as the NF-κB pathway. These findings provide a scientific rationale for an anti-inflammatory therapeutic and a template for a new HMG-CoA reductase inhibitor to produce a potential anti-hyperlipidemia agent.