Identification of N-benzyltetrahydroisoquinolines as novel anti-neuroinflammatory agents

Bioorg Med Chem. 2018 Nov 15;26(21):5711-5717. doi: 10.1016/j.bmc.2018.10.020. Epub 2018 Oct 22.

Abstract

A series of simplified berberine analogs was designed, synthesized, and evaluated for anti-inflammatory activity. SAR studies identified N-benzyltetrahydroisoquinoline 7d as a potent berberine analog. 7d suppressed LPS-induced inflammatory cytokine levels in both BV2 cells and primary microglia. Taken together, our results suggest that simplified BB analogs have therapeutic potential as a novel class of anti-neuroinflammatory agents.

Keywords: Berberine; Multiple sclerosis; Neuroinflammation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / chemical synthesis
  • Anti-Inflammatory Agents / chemistry
  • Anti-Inflammatory Agents / pharmacology*
  • Cell Line, Transformed
  • Cytokines / metabolism
  • Inflammation / chemically induced
  • Lipopolysaccharides
  • Mice
  • Microglia / drug effects
  • Molecular Conformation
  • Neuroprotective Agents / chemical synthesis
  • Neuroprotective Agents / chemistry
  • Neuroprotective Agents / pharmacology*
  • Structure-Activity Relationship
  • Tetrahydroisoquinolines / chemical synthesis
  • Tetrahydroisoquinolines / chemistry
  • Tetrahydroisoquinolines / pharmacology*

Substances

  • Anti-Inflammatory Agents
  • Cytokines
  • Lipopolysaccharides
  • Neuroprotective Agents
  • Tetrahydroisoquinolines