Synthesis and paroxonase activities of novel bromophenols

J Enzyme Inhib Med Chem. 2013 Oct;28(5):1073-9. doi: 10.3109/14756366.2012.715287. Epub 2012 Sep 20.

Abstract

Three novel bromophenols 10-12 were synthesized. Acylation of veratrole (4) with 2,3-dimethoxy benzoic acid (5) gave a kown diarylmethanone 6. Bromination of 6 with different equivalents of molecular bromine afforded new di and tribrominated compounds 7-9 which were converted to their corresponding bromophenols 10-12 via O-demethylation with BBr3. Paraoxonase-1 (PON1) was purified from human serum with approximately 42% and 3584 U × mg(-1) specific activity. The synthesized compounds 6-12 showed inhibitory effects on paraoxonase-1 (PON1) which is an organophosphate (OP) hydrolyser and an antioxidant bioscavenger enzyme. IC50 values were determined in the range of 0.123-1.212 mM.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aryldialkylphosphatase / antagonists & inhibitors*
  • Aryldialkylphosphatase / isolation & purification
  • Aryldialkylphosphatase / metabolism
  • Dose-Response Relationship, Drug
  • Enzyme Activation / drug effects
  • Enzyme Inhibitors / chemical synthesis
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology*
  • Humans
  • Molecular Structure
  • Phenols / chemical synthesis
  • Phenols / chemistry
  • Phenols / pharmacology*
  • Structure-Activity Relationship

Substances

  • Enzyme Inhibitors
  • Phenols
  • Aryldialkylphosphatase
  • PON1 protein, human