Calcium Channel Blockers: The Effect of Glutathione S‐Transferase Enzyme Activity and Molecular Docking Studies. Issue 40 (26th October 2021)

• Record Type: Journal Article
• Authors: Türkeş, Cüneyt; Kesebir, Arzu Öztürk; Demir, Yeliz; Küfrevioğlu, Ömer İrfan; Beydemir, Şükrü
• Is Part Of: ChemistrySelect. Volume 6:Issue 40(2021)
• Page Start: 11137
• Page End: 11143
• Publication Date: 2021-10-26
• Subjects: Biological Activity -- Calcium Channel Blockers -- Enzymes -- Glutathione S-Transferase -- Inhibition; Chemistry -- Periodicals; 540.5
• DOI: 10.1002/slct.202103100
• Languages: English
• ISSNs: 2365-6549

Abstract

Abstract: Recently, as a drug target in cancer treatment, the superfamily of glutathione S‐transferase (GSTs, EC 2.5.1.18) have been invited considerable interest by scientists. In particular, as they are overexpressed in many human cancer cell lines, GSTs can catalyze the conjugation of the cellular nucleophile glutathione (GSH) with a wide range of electrophilic carcinogens toxins and drugs, meanwhile producing oxidative stress. For this purpose, the GST was purified by GSH‐agarose affinity chromatography, and some calcium channel blockers (CCBs), such as amlodipine, cinnarizine, isradipine, nifedipine, and nilvadipine, were assessed for their inhibitory actions against GST. The CCBs demonstrated micromolar levels inhibitory activity towards GST ( K I s spanning within the 98.84±0.53 μM–502.70±2.53 μM range). The best GST inhibitory activity was observed for the isradipine. Additionally, molecular docking study was performed for competitive inhibitor nilvadipine on GST to describe the possible interaction with the active site to confirm the inhibitory activity. Abstract : In this study, GST was purified by GSH‐agarose affinity chromatography technique, and some calcium channel blockers, including amlodipine, cinnarizine, isradipine, nifedipine, and nilvadipine, were assessed for their inhibitory actions against GST. Also, molecular docking study was performed for competitive inhibitor nilvadipine on GST with the active site to confirm the inhibitory activity.