Structure-based design, synthesis and preliminary anti-inflammatory activity of bolinaquinone analogues

Eur J Med Chem. 2011 Feb;46(2):488-96. doi: 10.1016/j.ejmech.2010.11.028. Epub 2010 Nov 24.

Abstract

As a part of our drug discovery efforts we developed a series of simplified derivatives of bolinaquinone (BLQ), a hydroxyquinone marine metabolite, showing potent anti-inflammatory activity. Thirteen new hydroxyquinone derivatives closely related to BLQ were synthesized and tested on mouse macrophage-like RAW 264.7 cell line in order to investigate their ability to modulate the production of Prostaglandin E2 (PGE2). This optimization process led to the identification of three strictly correlated compounds with comparable and higher inhibitory potency than BLQ on PGE2 production. To evaluate the affinity of BLQ and its analogues for hsPLA2, surface plasmon resonance (SPR) experiments were performed.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / chemical synthesis*
  • Anti-Inflammatory Agents, Non-Steroidal / chemistry
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
  • Cell Line
  • Cyclooxygenase 2 / biosynthesis
  • Cyclooxygenase 2 / metabolism
  • Dose-Response Relationship, Drug
  • Drug Design*
  • Humans
  • Lipopolysaccharides / pharmacology
  • Macrophages / drug effects
  • Macrophages / metabolism
  • Mice
  • Molecular Structure
  • Sesquiterpenes / chemistry*
  • Sesquiterpenes / pharmacology*
  • Stereoisomerism
  • Structure-Activity Relationship
  • Surface Plasmon Resonance

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Lipopolysaccharides
  • Sesquiterpenes
  • bolinaquinone
  • Ptgs2 protein, mouse
  • Cyclooxygenase 2