Article 2021 · 21 citations

Calcium Channel Blockers: The Effect of Glutathione S-Transferase Enzyme Activity and Molecular Docking Studies

Turkes, Cuneyt, Kesebir, Arzu Ozturk, Demir, Yeliz, Kufrevioglu, Omer Irfan, Beydemir, Sukru

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 mu M-502.70 +/- 2.53 mu M 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.

Keywords

Biological Activity Calcium Channel Blockers Enzymes Glutathione S-Transferase Inhibition PULMONARY-HYPERTENSION SECONDARY IN-VITRO BIOLOGICAL EVALUATION CARBONIC-ANHYDRASE ACCURATE DOCKING METAL-IONS INHIBITION PROTEIN SILICO GLIDE

WoS Categories

Chemistry, Multidisciplinary

Sustainable Development Goals

Good Health and Well-being

Citation

Journal: CHEMISTRYSELECT
Year: 2021
Volume: 6
Issue: 40
Pages: 11137-11143
ISSN: 2365-6549
DOI: 10.1002/slct.202103100
WoS UID: WOS:000711482000048

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