Design and synthesis of 4-O-methylhonokiol analogs as inhibitors of cyclooxygenase-2 (COX-2) and PGF₁ production

Bioorg Med Chem. 2012 May 1;20(9):2860-8. doi: 10.1016/j.bmc.2012.03.028. Epub 2012 Mar 24.

Abstract

A series of novel 4-O-methylhonokiol analogs were synthesized in light of revealing structure-activity relationship for inhibitory effect of COX-2 enzyme. The key strategy of the molecular design was oriented towards modification of the potential metabolic soft spots (e.g., phenol and olefin) or by altering the polar surface area via incorporating heterocycles such as isoxazole and triazole. Most of all exhibited the inhibitory effects on COX-2 and PGF(1) production but not macrophage NO production. Especially, aryl carbamates 10 and 11 exhibited more potent inhibitory activity against COX-2 and PGF(1) production.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biphenyl Compounds / chemical synthesis
  • Biphenyl Compounds / chemistry*
  • Biphenyl Compounds / pharmacology*
  • Cell Line
  • Cell Survival / drug effects
  • Cyclooxygenase 2 / chemistry*
  • Cyclooxygenase 2 / metabolism
  • Cyclooxygenase 2 Inhibitors / chemical synthesis*
  • Cyclooxygenase 2 Inhibitors / chemistry
  • Cyclooxygenase 2 Inhibitors / pharmacology*
  • Drug Design*
  • Enzyme Activation / drug effects
  • Lignans / chemical synthesis
  • Lignans / chemistry*
  • Lignans / pharmacology*
  • Macrophages / drug effects
  • Macrophages / metabolism
  • Mice
  • Nitric Oxide / metabolism
  • Prostaglandins F / metabolism*
  • Structure-Activity Relationship

Substances

  • 4-O-methylhonokiol
  • Biphenyl Compounds
  • Cyclooxygenase 2 Inhibitors
  • Lignans
  • Prostaglandins F
  • Nitric Oxide
  • Cyclooxygenase 2
  • prostaglandin F1