2,3-Dihydroxy-quinoxaline induces ATPase activity of Herpes Simplex Virus thymidine kinase

FEBS Lett. 2014 Jan 31;588(3):509-11. doi: 10.1016/j.febslet.2013.12.017. Epub 2013 Dec 25.

Abstract

2,3-Dihydroxy-quinoxaline, a small molecule that promotes ATPase catalytic activity of Herpes Simplex Virus thymidine kinase (HSV-TK), was identified by virtual screening. This compound competitively inhibited HSV-TK catalyzed phosphorylation of acyclovir with Ki=250 μM (95% CI: 106-405 μM) and dose-dependently increased the rate of the ATP hydrolysis with KM=112 μM (95% CI: 28-195 μM). The kinetic scheme consistent with this experimental data is proposed.

Keywords: 2,3-dihydroxy-quinoxaline; DHQ; Enzyme kinetic; HSV-TK; Herpes Simplex Virus thymidine kinase; Inhibition; Molecular docking; TLC; Thymidine kinase; thin layer chromatography.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acyclovir / therapeutic use
  • Adenosine Triphosphatases / chemistry*
  • Catalysis
  • Humans
  • Kinetics
  • Phosphorylation / drug effects
  • Quinoxalines / pharmacology*
  • Simplexvirus / drug effects
  • Simplexvirus / enzymology*
  • Thymidine Kinase / antagonists & inhibitors*
  • Thymidine Kinase / chemistry

Substances

  • Quinoxalines
  • 2,3-dihydroxyquinoxaline
  • Thymidine Kinase
  • Adenosine Triphosphatases
  • Acyclovir