Inhibition of Paraoxonase 1 by Coumarin-Substituted N-Heterocyclic Carbene Silver(I), Ruthenium(II) and Palladium(II) Complexes

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 IC<inf>50</inf> value of 3.01 μM 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. © 2019 John Wiley & Sons, Ltd.