A potential risk factor for paraoxonase 1: in silico and in-vitro analysis of the biological activity of proton-pump inhibitors


Türkeş C.

JOURNAL OF PHARMACY AND PHARMACOLOGY, vol.71, no.10, pp.1553-1564, 2019 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 71 Issue: 10
  • Publication Date: 2019
  • Doi Number: 10.1111/jphp.13141
  • Journal Name: JOURNAL OF PHARMACY AND PHARMACOLOGY
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Page Numbers: pp.1553-1564
  • Keywords: coronary artery diseases, HDL, inhibition, molecular docking, paraoxonase, proton-pump inhibitor, HIGH-DENSITY-LIPOPROTEIN, CORONARY-ARTERY-DISEASE, HUMAN SERUM PARAOXONASE-1, PON1 ACTIVITY, PROTEIN, PURIFICATION, ASSOCIATION, CALCIUM, ENZYMES, HDL
  • Erzincan Binali Yildirim University Affiliated: Yes

Abstract

Objectives Proton-pump inhibitors (PPIs) are drugs commonly utilized by about 7% of adults in the world. Recent researches have shown that there are countless and severe side effects of these drugs. This situation has raised concern among clinicians and patients alike. The purpose of this study is to contribute the novel drug discovery and development technology and toxicology field by researching interactions of PPIs on paraoxonase 1. Methods In this study, the paraoxonase 1 enzyme was purified from human serum by using rapid and straightforward chromatographic techniques. Subsequently, the inhibition effects of pantoprazole, omeprazole, and esomeprazole, PPIs, were investigated on paraoxonase 1. Besides, molecular docking studies were performed to unravel the binding mechanism between the enzyme and drugs. Key findings All drugs showed potent inhibitory activities. IC50 of the drugs values were 54.780 +/- 0.524, 86.470 +/- 0.818 and 93.390 +/- 0.885 mm and K-i constants were found as 39.895 +/- 0.005 mm, 70.112 +/- 0.010 mm and 78.868 +/- 0.008 mm, respectively. The binding scores observed in silico studies were found to agree with the obtained from in-vitro experimental results. Conclusions We observed that the drugs decreased PON1 activity at low concentrations. The results show that adjusting the dosages of these medications is a crucial case for each patient. The physicians should more carefully interpret whether there is an essential indication before prescribing PPIs and, if there is, to approve the proper dosing for the situation.