Curvularin derivatives from hydrothermal vent sediment fungus Penicillium sp. HL-50 guided by molecular networking and their anti-inflammatory activity

With the guidance of molecular networking, nine new curvularin derivatives ( 1 - 9 ) and 16 known analogues ( 10-25 ) were discovered from a hydrothermal vent sediment fungus Penicillium sp. HL-50, in which compounds 5 - 7 were a hybrid of curvularin and purine. The planar structures of compounds 1-9 and their absolute configurations were determined by detailed analyses of NMR, X-ray diffraction, electronic circular dichroism (ECD) calculations, ¹³C NMR calculation, modified Mosher’s method, and chemical derivatization. Anti-inflammatory activities investigation revealed that compounds 7 - 9 , 11 , 12 , 14 , 15 , and 18 showed significantly suppressive effects against LPS-induced nitric oxide (NO) production on murine macrophage RAW264.7 with IC₅₀ values ranging from 0.44 to 4.40 μM. Also, we found that these bioactive compounds could suppress the expression of inflammation-related proteins including iNOS, COX-2, NLRP3, and NF-κB. Further study proved new compound 7 possessed strong anti-inflammatory activity by inhibiting the transcription of inflammation-related genes, downregulating the expression of inflammation-related proteins, and inhibiting the release of inflammatory cytokines, suggesting its potential application in the treatment of inflammatory diseases.