In vitro inhibition effect of some coumarin compounds on purified human serum paraoxonase 1 (PON1)

J Enzyme Inhib Med Chem. 2016 Aug;31(4):534-7. doi: 10.3109/14756366.2015.1043297. Epub 2015 May 18.

Abstract

Human serum paraoxonase 1 (PON1; EC 3.1.8.1) is a high-density lipoprotein associated, calcium-dependent enzyme that hydrolyses aromatic esters, organophosphates and lactones and can protect the low-density lipoprotein against oxidation. In this study, in vitro effect of some hydroxy and dihydroxy ionic coumarin derivatives (1-20) on purified PON1 activity was investigated. Among these compounds, derivatives 11-20 are water soluble. In investigated compounds, compounds 6 and 13 were found the most active (IC50 = 35 and 34 µM) for PON1, respectively. The present study has demonstrated that PON1 activity is very highly sensitive to studied coumarin derivatives.

Keywords: Coumarin derivatives; in vitro inhibition; paraoxonase.

MeSH terms

  • Aryldialkylphosphatase / antagonists & inhibitors*
  • Aryldialkylphosphatase / isolation & purification
  • Aryldialkylphosphatase / metabolism
  • Coumarins / chemical synthesis
  • Coumarins / chemistry
  • Coumarins / pharmacology*
  • Dose-Response Relationship, Drug
  • Enzyme Inhibitors / chemical synthesis
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology*
  • Humans
  • Inhibitory Concentration 50
  • Molecular Structure
  • Structure-Activity Relationship

Substances

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