Molecular Insight of the Possible Inhibition Mechanism of Therapeutic Cephalosporin Derivatives against Human Glutathione Reductase Enzyme

Abstract

Glutathione reductase is a key enzyme for glutathione metabolism. Inhibition of the enzyme activity related to various health problems. Therefore, determination of inhibitors of the enzyme and its possible inhibition mechanism are quite important. Some cephalosporins have exhibited potent inhibitory effect against human glutathione reductase (hGR). In order to understand the inhibition mechanism of the cephalosporins, we carried out molecular docking studies with Glide docking and Induced-fit Docking methods. Binding sites of hGR were predicted and the best suitable binding site of the drugs was identified with the Glide docking method. The binding affinity of the drugs was calculated with the induced-fit docking method. The best binding site of the drugs was detected as a part of the catalytic active site for Cefoperazone, Cefodizime, and Ceftazidime, dimerization site for Cefotaxime, Ceftriaxone, and Cefuroxime, and aromate binding site for Ceftizoxime. The Binding affinity of the Cefoperazone was calculated as -10.643 kcal/mol. The results have indicated that hGR enzyme would be inhibited with different mechanisms because of its several druggable sites. These findings would be helpful for designing new inhibitors for hGR enzyme and understanding of potential inhibition mechanism of its other known inhibitors.