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).
Keywords: Anti-inflammatory; Azaphilones; Mangrove endophytic fungus; Penicillium sclerotiorum.
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