摘要Guided by molecular networking,nine novel curvularin derivatives(1-9)and 16 known ana-logs(10-25)were isolated from the hydrothermal vent sediment fungus Penicillium sp.HL-50.Notably,compounds 5-7 represented a hybrid of curvularin and purine.The structures and absolute configurations of compounds 1-9 were elucidated via nuclear magnetic reson-ance(NMR)spectroscopy,X-ray diffraction,electronic circular dichroism(ECD)calculations,13C NMR calculation,modified Mosher's method,and chemical derivatization.Investigation of anti-inflammatory activities revealed that compounds 7-9,11,12,14,15,and 18 exhibited significant suppressive effects against lipopolysaccharide(LPS)-induced nitric oxide(NO)production in murine macrophage RAW264.7 cells,with IC50 values ranging from 0.44 to 4.40μmol·L-1.Furthermore,these bioactive compounds were found to suppress the expression of inflammation-related proteins,including inducible NO synthase(iNOS),cyclooxygenase-2(COX-2),NLR family pyrin domain-containing protein 3(NLRP3),and nuclear factor kappa-B(NF-κB).Additional studies demonstrated that the novel compound 7 possessed potent anti-inflammatory activity by inhibiting the transcription of inflammation-related genes,downreg-ulating the expression of inflammation-related proteins,and inhibiting the release of inflam-matory cytokines,indicating its potential application in the treatment of inflammatory dis-eases.