Synthesis and biological evaluation of novel schisanhenol derivatives as potential hepatoprotective agents

Eur J Med Chem. 2022 Jan 5:227:113919. doi: 10.1016/j.ejmech.2021.113919. Epub 2021 Oct 12.

Abstract

Twenty-one new schisanhenol derivatives were synthesized, and their hepatoprotective effects against liver injury induced by concanavalin A (Con A) were evaluated in vitro using an MTT assay. The data indicated that most derivatives exhibited equivalent or better protective activity than the positive control (dimethyl dicarboxylate biphenyl, DDB) under the same conditions. Among them, compound 1b showed the most potent hepatoprotective activity against Con A-induced immunological injury. Mechanistic studies in vitro revealed that 1b inhibited cell apoptosis and inflammatory responses caused by Con A treatment via IL-6/JAK2/STAT3 signaling pathway. Consistently, it also exhibited significant hepatoprotective activity in mice with Con A-induced immunological liver injury. These results clearly indicated that 1b might be a highly potent hepatoprotective agent targeting IL-6/STAT3 signaling pathway.

Keywords: Apoptosis; Concanavalin A; Hepatoprotective activity; IL-6/JAK2/STAT3 signaling pathway; Immunological liver injury; Schisanhenol derivatives.

MeSH terms

  • Animals
  • Cells, Cultured
  • Chemical and Drug Induced Liver Injury / drug therapy*
  • Chemical and Drug Induced Liver Injury / metabolism
  • Chemical and Drug Induced Liver Injury / pathology
  • Concanavalin A
  • Cyclooctanes / chemical synthesis
  • Cyclooctanes / chemistry
  • Cyclooctanes / pharmacology*
  • Dose-Response Relationship, Drug
  • Female
  • Humans
  • Interleukin-6 / antagonists & inhibitors
  • Interleukin-6 / blood
  • Interleukin-6 / metabolism
  • Liver / drug effects*
  • Liver / metabolism
  • Liver / pathology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Molecular Structure
  • Polycyclic Compounds / chemical synthesis
  • Polycyclic Compounds / chemistry
  • Polycyclic Compounds / pharmacology*
  • Protective Agents / chemical synthesis
  • Protective Agents / chemistry
  • Protective Agents / pharmacology*
  • STAT3 Transcription Factor / antagonists & inhibitors
  • STAT3 Transcription Factor / metabolism
  • Signal Transduction / drug effects
  • Structure-Activity Relationship

Substances

  • Cyclooctanes
  • Interleukin-6
  • Polycyclic Compounds
  • Protective Agents
  • STAT3 Transcription Factor
  • Stat3 protein, mouse
  • Concanavalin A
  • schisanhenol