Journal of Ata-Chem (Jun 2023)
Some phenolic compounds as inhibitors of glutathione s-transferase and glutathione reductase: an in vitro and in silico analysis
Abstract
It has been determined that Glutathione S-transferases (GSTs) and Glutathione reductase (GR) activities increase in cancer cells and contribute to the progression of cancer by causing multidrug resistance (MDR). Glutathione reductase catalyzes electron transfer between oxidized glutathione (GSSG) and nicotinamide adenine dinucleotide phosphate, reduced form, (NADPH). The reduced glutathione (GSH) formed as a result of this reaction detoxifies various xenobiotics by attacking the electrophilic center in the catalysis of GSTs. Detoxification of anticancer drugs with increased expression of GST and GR in cancer cells reduces the effectiveness of these drugs. Therefore, GST and GR inhibition is an important approach in cancer treatments. In this study, from human erythrocytes, GR was isolated by using 2',5'-ADP Sepharose 4B affinity chromatography method with 16.912 EU/mg protein specific activity, and GST was isolated by using Glutathione Agarose affinity chromatography method with 4.88 EU/mg protein specific activity. After the isolation of the enzymes, the inhibition effects of vanillin, epicatechin, and catechin on the activities were investigated. While all three substances did not inhibit GST, vanillin and epicatechin were found to inhibit GR with IC50 values of 86.25 μM and 345 μM, respectively. The elucidation of the inhibition mechanism was carried out by molecular docking studies using the AutoDock program.
