Аңдатпа
Context: Paraoxonase 1 (PON1) is a crucial antioxidant enzyme involved in the hydrolysis of organophosphates and the prevention of oxidative damage to lipoproteins. Objective: This study aimed to purify PON1 using a newly synthesised hydrophobic interaction chromatography gel and to investigate the inhibitory effects of selected emergency cardiac drugs on PON1 activity through in vitro and in silico approaches. Materials and methods: PON1 was purified using a Sepharose-4B-L-tyrosine-6-aminochrysene hydrophobic interaction chromatography gel. The inhibitory effects of deslanoside, digitoxin, esmolol, and adenosine were evaluated via kinetic inhibition assays, molecular docking, molecular dynamics simulations, and MMPBSA calculations. Results: Among the tested compounds, esmolol exhibited the strongest inhibition of PON1 activity (IC50 = 0.131 ± 0.071 μM, Ki = 0.044 ± 0.009 μM) via a competitive mechanism. Molecular docking revealed strong binding affinity of esmolol to the PON1 active site, which was further supported by molecular dynamics simulations over 150 ns. Discussion and conclusion: The findings indicate a potential interaction between commonly used emergency cardiac drugs and PON1, highlighting the importance of evaluating off-target effects on critical metabolic enzymes in cardiovascular therapy.