Chemistry Department, Faculty of Science, Atatürk University, Erzurum, Turkey.
Molecular Biology and Genetics Department, Faculty of Arts and Science, Kilis 7 Aralık University, Kilis, Turkey.
J Biomol Struct Dyn. 2021 Mar;39(5):1744-1753. doi: 10.1080/07391102.2020.1738962. Epub 2020 Mar 16.
Glutathione reductase (GR) is a major antioxidant enzyme essential to maintain GSH/GSSG ratio by catalyzing recovery of reduced glutathione (GSH) from oxidized glutathione (GSSG). Because of this vital task, the inhibition of GR is an important target in the treatment of many diseases, so we aimed to identify natural and new GR inhibitors to be guide for drug design.For this purpose, two different approaches were used. The first one is inhibition, the first phase of which was the purification of the enzyme from human erythrocyte by 2', 5'-ADP Sepharose 4B affinity chromatography, and then the inhibition effects of curcumin, quercetin, and resveratrol were examined. The second one is study, which was performed to elucidate the drug-likeness, active site identification and inhibition mechanisms of these compounds.hGR was isolated from human erythrocytes with 7.036 EU/mg protein specific activity and 48.97% yield. Then, IC values were as 17.25 ± 3.8 µM, 57.8 ± 14.2 µM, and 520 ± 96.7 µM for curcumin, quercetin, and resveratrol respectively. Docking studies of compounds were performed against hGR receptors with induced-fit docking method. The compound showed Glide score as 10.519 kcal/mol, -9.789, and -8.133 respectively.In conclusion, it was seen that curcumin is the much better inhibitor than quercetin and resveratrol for hGR according to both and studies. Curcumin, a potential inhibitor of hGR, can be used in drug design to target the glutathione system in cellular injury.Communicated by Ramaswamy H. Sarma.
谷胱甘肽还原酶（GR）是一种重要的抗氧化酶，通过催化还原型谷胱甘肽（GSH）从氧化型谷胱甘肽（GSSG）中恢复，对维持 GSH/GSSG 比值至关重要。由于这个重要的任务，GR 的抑制是治疗许多疾病的重要目标，因此我们旨在确定天然和新型 GR 抑制剂，为药物设计提供指导。为此，我们采用了两种不同的方法。第一种是抑制法，第一阶段是通过 2'，5'-ADP Sepharose 4B 亲和层析从人红细胞中纯化酶，然后研究姜黄素、槲皮素和白藜芦醇的 抑制作用。第二种是 研究，用于阐明这些化合物的药物相似性、活性位点识别和抑制机制。hGR 从人红细胞中分离出来，比活 7.036 EU/mg 蛋白，得率 48.97%。然后，IC 值分别为 17.25 ± 3.8 μM、57.8 ± 14.2 μM 和 520 ± 96.7 μM 对于姜黄素、槲皮素和白藜芦醇。用诱导契合对接方法对化合物进行 hGR 受体对接研究。该化合物的 Glide 评分分别为 10.519 kcal/mol、-9.789 和-8.133。综上所述，根据 抑制和 研究，姜黄素对 hGR 的抑制作用明显优于槲皮素和白藜芦醇。姜黄素作为 hGR 的潜在抑制剂，可用于药物设计，靶向细胞损伤中的谷胱甘肽系统。由 Ramaswamy H. Sarma 传达。
