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

Chin J Nat Med. 2025 Jan;23(1):119-128. doi: 10.1016/S1875-5364(25)60803-X.

Abstract

Guided by molecular networking, nine novel curvularin derivatives (1-9) and 16 known analogs (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 resonance (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 4.40 μmol·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, downregulating the expression of inflammation-related proteins, and inhibiting the release of inflammatory cytokines, indicating its potential application in the treatment of inflammatory diseases.

Keywords: Anti-inflammatory activity; Curvularin derivatives; Molecular networking; Penicillium sp. HL-50.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents* / chemistry
  • Anti-Inflammatory Agents* / pharmacology
  • Cyclooxygenase 2 / genetics
  • Cyclooxygenase 2 / metabolism
  • Hydrothermal Vents / microbiology
  • Lipopolysaccharides / pharmacology
  • Macrophages / drug effects
  • Mice
  • Molecular Structure
  • NF-kappa B / metabolism
  • NLR Family, Pyrin Domain-Containing 3 Protein / genetics
  • NLR Family, Pyrin Domain-Containing 3 Protein / metabolism
  • Nitric Oxide Synthase Type II* / genetics
  • Nitric Oxide Synthase Type II* / metabolism
  • Nitric Oxide* / metabolism
  • Penicillium* / chemistry
  • RAW 264.7 Cells
  • Zearalenone / analogs & derivatives

Substances

  • Anti-Inflammatory Agents
  • Nitric Oxide
  • Nitric Oxide Synthase Type II
  • curvularin
  • NF-kappa B
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • Cyclooxygenase 2
  • Lipopolysaccharides
  • Zearalenone