Some calcium-channel blockers: kinetic andin silicostudies on paraoxonase-I


JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS, vol.40, no.1, pp.77-85, 2022 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 40 Issue: 1
  • Publication Date: 2022
  • Doi Number: 10.1080/07391102.2020.1806927
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, BIOSIS, CAB Abstracts, Chemical Abstracts Core, EMBASE, MEDLINE
  • Page Numbers: pp.77-85
  • Keywords: Paraoxonase, HDL, chromatography, inhibition, calcium-channel blocker, molecular docking, ACCURATE DOCKING, PROTEIN, PHARMACOKINETICS, PURIFICATION, VITRO, PON1, HYDROCHLORIDE, PREDICTION, MOLECULES, DESIGN
  • Anadolu University Affiliated: Yes


Many drugs, which are used in clinical treatments, show pharmacological effects on enzyme activity with an essential role in the pathogenesis of various diseases. Paraoxonase-I (PON1) is a member of the mammalian lactonase enzyme family, serves to the prevention of blood vessel plaque formation by protecting high-density lipoprotein and low-density lipoprotein against oxidation. In the current study, we aimed to contribute to drug discovery and to determine the interaction of some calcium channel blockers (CCBs) with PON1. For this purpose, first, the PON1 enzyme was purified from fresh human serum by using different chromatographic techniques. Then, the various concentrations of CCBs were tested on the paraoxonase activity of PON1.IC(50)values were found as 41.00, 48.00, and 180 mu M for nimodipine, cinnarizine, and nilvadipine, respectively. PON1 was effectively inhibited by these drugs (K(i)s ranging between 22.13 +/- 1.13 and 174.12 +/- 20.52 mu M). Of these drugs, only the inhibition mechanism of cinnarizine was competitive on PON1. Besides, the molecular docking analysis of cinnarizine was applied to detailed the binding interactions on the active site of PON1. The docking scores for the Glide standard-precision (SP), and Glide extra-precision (XP) modes for 1V04 receptor monitored to be -5.001, and -6.079, respectively. We determined that the CCBs reduced PON1 enzyme activity bothin vitroandin silicoconditions, significantly. Therefore, further biological studies such as gene expression andin vivoexperiments should be done for these drugs. Communicated by Ramaswamy H. Sarma