In vitro effects of thirty-eight cardiac drugs on human serum paraoxonase

Abstract

In this study, the effects of 38 commonly used cardiac drugs on the human paraoxonase (PON1) were investigated. PON1 was purified from human serum blood by ammonium sulfate precipitation (60%-80%) and hydrophobic interaction chromatography (Sepharose-4B similar to L-tyrosine-1-napthylamine gel). All of the cardiac drugs inhibited PON1 at the micro molar level. IC50 and K-i values were determined for each drug. The tested drugs displayed potent PON1 inhibitory activity. It was found that the weakest PON1 inhibitors are Irbesartan (K-i: 421.73 mu M), Glyceryl Trinitrate (K-i: 351.48 RM), and Apixaban (K-i: 333.27 mu M). Bisoprolol hemifumarate (k(i): 269.31 mu M) is also other weak PON1 inhibitor. Therefore, these drugs, having weak PON1 inhibitory activity, may be preferred primarily in patients with atheroclerotic heart disease compared to other drugs due

to the protective effect of PON1 on atherosclerosis. Conversely, the most potent inhibitors against PON1 were propafenone (K-i: 0.35 mu M), lacidipine (K-i: 0.78 mu M), I,idocaine HCl (K-i: 1.78 mu M), and Propranolol (K-i : 1.86 mu M). Molecular docking was also applied to confirm the activity of some cardiac drugs on PON1.