Asperiecolins A-D: Undescribed Variecolin-Type Sesterterpenoids with Anti-Inflammatory and AChE Inhibitory Activities from Aspergillus sp. TJ403-YJ22

J Org Chem. 2026 Apr 24;91(16):5723-5729. doi: 10.1021/acs.joc.6c00291. Epub 2026 Apr 15.

Abstract

Four new sesterterpenoids, designated as asperiecolins A-D (1-4), were isolated from fungus Aspergillus sp. TJ403-YJ22. Asperiecolin A (1) possesses an unprecedented 5/8/6/6/5-fused pentacyclic framework with 11 stereocenters, while asperiecolins B (2) and C (3) feature an unusual five-membered lactam ring. All compounds inhibited LPS-induced NO and TNF-α production in macrophages. Additionally, compound 1 exhibited potent AChE inhibition (IC50 = 0.67 ± 0.05 μM), highlighting its therapeutic potential for inflammatory and neurodegenerative diseases.

MeSH terms

  • Acetylcholinesterase* / metabolism
  • Animals
  • Anti-Inflammatory Agents* / chemistry
  • Anti-Inflammatory Agents* / isolation & purification
  • Anti-Inflammatory Agents* / pharmacology
  • Anti-Inflammatory Agents, Non-Steroidal* / chemistry
  • Anti-Inflammatory Agents, Non-Steroidal* / isolation & purification
  • Anti-Inflammatory Agents, Non-Steroidal* / pharmacology
  • Aspergillus* / chemistry
  • Cholinesterase Inhibitors* / chemistry
  • Cholinesterase Inhibitors* / isolation & purification
  • Cholinesterase Inhibitors* / pharmacology
  • Lipopolysaccharides / antagonists & inhibitors
  • Lipopolysaccharides / pharmacology
  • Macrophages / drug effects
  • Macrophages / metabolism
  • Mice
  • Molecular Structure
  • Nitric Oxide / antagonists & inhibitors
  • Nitric Oxide / biosynthesis
  • RAW 264.7 Cells
  • Sesterterpenes* / chemistry
  • Sesterterpenes* / isolation & purification
  • Sesterterpenes* / pharmacology
  • Structure-Activity Relationship
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors
  • Tumor Necrosis Factor-alpha / biosynthesis

Substances

  • Sesterterpenes
  • Tumor Necrosis Factor-alpha
  • Cholinesterase Inhibitors
  • Nitric Oxide
  • Lipopolysaccharides
  • Anti-Inflammatory Agents
  • Acetylcholinesterase
  • Anti-Inflammatory Agents, Non-Steroidal