Inhibition of paraoxonase 1 by coumarin-substituted N-heterocyclic carbene silver(I), ruthenium(II) and palladium(II) complexes

KARATAŞ M. O., Calgin G., ALICI B., GÖKÇE B., GENÇER N., TAŞKIN TOK T., ...More

APPLIED ORGANOMETALLIC CHEMISTRY, vol.33, no.10, 2019 (SCI-Expanded) identifier identifier

  • Publication Type: Article / Article
  • Volume: 33 Issue: 10
  • Publication Date: 2019
  • Doi Number: 10.1002/aoc.5130
  • Journal Name: APPLIED ORGANOMETALLIC CHEMISTRY
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Keywords: coumarin, inhibition, N-heterocyclic carbenes, paraoxonase 1, HUMAN SERUM PARAOXONASE, PD-PEPPSI COMPLEXES, IN-VITRO, CRYSTAL-STRUCTURES, ANTICANCER, PON1, PURIFICATION, ARYLESTERASE, IMIDAZOLIUM, LIGANDS
  • Ondokuz Mayıs University Affiliated: Yes

Abstract

We synthesized three coumarin-substituted benzimidazolium chlorides and their silver(I), ruthenium(II) and palladium(II) N-heterocyclic carbene (NHC) complexes. All compounds were characterized using appropriate spectroscopic techniques and elemental analyses. Single-crystal X-ray structure of a Pd(II)-NHC complex (6b) was also determined. The inhibitory properties of all compounds were tested on the activity of human paraoxonase 1 (PON1). All complexes exhibited weaker inhibitory properties than their corresponding benzimidazolium salts except for complex 6b which is the most active inhibitor with an IC50 value of 3.01 mu M among the compounds reported in this study. A kinetic evaluation showed that this complex inhibits PON1 activity in a non-competitive manner. Molecular docking studies were also performed for 6b in order to obtain more insight into the binding mode.