摘要Two novel diketopiperazines(1 and 5),along with ten known compounds(2-4,6-12)demonstrating significant skin inflammation inhibition,were isolated from a marine-derived fungus identified as Aspergillus sp.FAZW0001.The structural elucidation and configurational reassessments of compounds 1-5 were established through comprehensive spectral analyses,with their absolute configurations determined via single crystal X-ray diffraction using Cu Kαradiation,Marfey's method,and comparison between experimental and calculated electronic circular dichroism(ECD)spectra.Compounds 1,2,and 8 exhibited significant anti-inflammat-ory activities in Propionibacterium acnes(P.acnes)-induced human monocyte cell lines.Com-pound 8 demonstrated the ability to down-regulate interleukin-1β(IL-1β)expression by in-hibiting Toll-like receptor 2(TLR2)expression and modulating the activation of myeloid dif-ferentiation factor 88(MyD88),mitogen-activated protein kinase(MAPK),and nuclear factorκB(NF-κB)signaling pathways,thus reducing the cellular inflammatory response induced by P.acnes.Additionally,compound 8 showed the capacity to suppress mitochondrial reactive oxygen species(ROS)production and nucleotide-binding oligomerization domain-like recept-or protein 3(NLRP3)inflammasome activation,thereby reducing IL-1β maturation and secre-tion.A three-dimensional quantitative structure-activity relationships(3D-QSAR)model was applied to compounds 5-12 to analyze their anti-inflammatory structure-activity relation-ships.