Peniazaphilones A—I, Produced by Co‐culturing of Mangrove Endophytic Fungi, Penicillium sclerotiorumTHSH‐4 and Penicillium sclerotiorumZJHJJ‐18

Main observation and conclusion 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, 13 C 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 (IC 50 = 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 (IC 50 = 35.27 μmol/L). Moreover, compounds 1 and 13 displayed moderate to strong cytotoxicity to A549 and MDA‐MB‐435, with IC 50 values in the range of 6.84—14.63 μmol/L. Together compound 1 showed moderate broad‐spectrum antibacterial activity.