Inhibition of Na+/K+-ATPase by 5,6,7,8-tetrafluoro-3-hydroxy-2-phenylquinolin-4(1H)-one

Biochimie. 2017 Jul:138:56-61. doi: 10.1016/j.biochi.2017.04.009. Epub 2017 Apr 20.

Abstract

Na+/K+-ATPase (NKA) is an enzyme of crucial importance for all animal cells. We examined the inhibitory effects of halogenated phenylquinolinones on NKA. The 5,6,7,8-tetrafluoro-3-hydroxy-2-phenylquinolin-4(1H)-one (TFHPQ) was identified as an efficient NKA inhibitor with IC50 near 10 μM. The inhibition by TFHPQ is particularly efficient at higher concentrations of K+, where NKA adopts the E2 conformation. The experimental observations are in a good agreement with the outcomes from molecular docking. We identified an energetically favourable TFHPQ binding site for the K+-bound NKA, which is located in the proximity of the cytoplasmic C-terminus.

Keywords: Binding sites; Inhibition; Na(+)/K(+)-ATPase; Quinolinones; Sodium pump.

MeSH terms

  • Animals
  • Binding Sites
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology*
  • Molecular Docking Simulation*
  • Protein Structure, Tertiary
  • Quinolones / chemistry
  • Quinolones / pharmacology*
  • Sodium-Potassium-Exchanging ATPase / antagonists & inhibitors*
  • Sodium-Potassium-Exchanging ATPase / chemistry
  • Sodium-Potassium-Exchanging ATPase / metabolism
  • Swine / metabolism

Substances

  • 5,6,7,8-tetrafluoro-3-hydroxy-2-phenylquinolin-4(1H)-one
  • Enzyme Inhibitors
  • Quinolones
  • Sodium-Potassium-Exchanging ATPase