Azaphilone derivatives with anti-inflammatory activity from the mangrove endophytic fungus Penicillium sclerotiorum ZJHJJ-18

Nine undescribed azaphilone derivatives, sclerazaphilones A–H (1–9), and three known analogues (10–12), were obtained and identified from the fermented rice cultures of a mangrove endophytic fungus Penicillium sclerotiorum ZJHJJ-18. 1D and 2D NMR, HRESIMS and spectral data indicated the chemical structures of 1–9, and their absolute configurations were assigned by experimental and computational analyses of electronic circular dichroism (ECD) spectra, and application of the chemical transformations. Compounds 1–4 were the first reported N-containing azaphilone derivatives with 5/6 dicyclic core. The bioassay results showed that compounds 3–5 exhibited effective inhibitory effects on the nitric oxide (NO) production in lipopolysaccharide (LPS)-induced RAW264.7 macrophage cells with IC50 values in the range of 6.30–9.45 μM. Moreover, a molecular docking study was conducted to investigate the probable binding interaction of 3–5 with inducible nitric oxide synthase (iNOS).