Evaluation of chalcones as inhibitors of glutathione S-transferase

J Biochem Mol Toxicol. 2018 May;32(5):e22047. doi: 10.1002/jbt.22047. Epub 2018 Feb 23.

Abstract

Glutathione S-transferases (GSTs) are the superfamily of multifunctional detoxification isoenzymes and play an important role in cellular signaling. In the present study, potential inhibition effects of chalcones were tested against human GST. For this purpose, GST was purified from human erythrocytes with 5.381 EU⋅mg-1 specific activity and 51.95% yield using a GSH-agarose affinity chromatographic method. The effects of chalcones on in vitro GST activity were tested at various concentrations. Ki constants of chalcones were found in the range of 7.76-41.93 μM. According to the results, 4-fluorochalcone showed a better inhibitory effect compared with the other compounds. The inhibition mechanisms of 2'-hydroxy-4-methoxychalcone and 4-methoxychalcone were noncompetitive, whereas the inhibition mechanisms of 4'- hydroxychalcone, 4- fluorochalcone, and 4,4'- diflurochalcone were competitive.

Keywords: chalcone; glutathione S-transferase; inhibition; purification.

MeSH terms

  • Chalcones / chemistry*
  • Drug Evaluation, Preclinical
  • Enzyme Inhibitors / chemistry*
  • Erythrocytes / enzymology*
  • Glutathione Transferase / antagonists & inhibitors*
  • Glutathione Transferase / chemistry*
  • Glutathione Transferase / isolation & purification
  • Humans

Substances

  • Chalcones
  • Enzyme Inhibitors
  • Glutathione Transferase