2-Quinolinone Derivatives as Potential Inhibitors of Glutathione-Related Enzymes

GÜLLER P. T., Körükmez M.

International Journal of Chemistry and Technology (IJCT), cilt.0, sa.10, ss.1-9, 2026 (TRDizin)

Özet

Glutathione, a thiol molecule, is necessary for healthy cells against oxidative stress and xenobiotics. Two glutathione-related enzymes glutathione reductase (GR) and glutathione S-transferase (GST) were studied in this paper. This study aimed to investigate the inhibitory potencies of 2-quinolinone derivatives on hGR and hGST and to reveal their structure–activity relationships by both kinetic and computational approaches. For this purpose, firstly, GST and GR were collected from human erythrocytes with specific activities of 8.78 EU/mg protein and 5.85 EU/mg protein. Then, inhibitory potencies of 2-quinolinone derivatives on hGR and hGST were assayed in vitro. IC50-[inhibitor] and Lineweaver-Burk graphs were generated. QU3, 6-hydroxy-2(h)-quinolinone, was found to be the most effective inhibitor against two enzymes with Ki values of 5.18±1.57 μM and 27.69±5.412 μM. Besides, binding energies of QU3 on hGR and hGST receptors were estimated as -5.59 kcal/mol and -5.81 kcal/mol. These findings suggest that the 2- quinolinone structure is a promising pharmacophore for use in new hGR and hGST assays. Future configuration modifications with higher selectivity and demonstrated efficacy are planned.