Peniazaphilones A—I,Produced by Co-culturing of Mangrove Endophytic Fungi,Penicillium sclerotiorum THSH-4 and Penicillium sclerotiorum ZJHJJ-18

摘要

Co-culturing the mangrove endophytic fungus Penicillium sclerotiorum THSH-4 with Penicillium sclerotiorum ZJHJJ-18 in PDB medium resulted in the production of nine new azaphilones derivatives,peniazaphilones A—I (1-9),and six known azaphilones derivatives(10-15).Their structures were elucidated by analysis of detailed spectroscopic data,single-crystal X-ray diffraction,ECD spectra,13C NMR calculation and DP4+ analysis.It is noteworthy that compound 1 with an isoquinoline quinone moiety,was isolated from natural source for the first time.Besides,compound 2 is the third reported phenylhydrazone derivative from fungi.In the bioactivity assays,compounds 1,12,14 and 15 (IC50 =4.71-17.64 μmol/L) exhibited potent inhibition of LPS-induced NO release from RAW264.7 without obvious cytotoxicity within 50 μmol/L compared to the positive control indomethacin (ICs0 =35.27 μmol/L).Moreover,com-pounds 1 and 13 displayed moderate to strong cytotoxicity to A549 and MDA-MB-435,with IC50 values in the range of 6.84-14.63μmol/L.Together compound 1 showed moderate broad-spectrum antibacterial activity.