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 enzymeactivity related to various health problems. Therefore, determination of inhibitors of theenzyme and its possible inhibition mechanism are quite important. Some cephalosporins haveexhibited potent inhibitory effect against human glutathione reductase (hGR). In order tounderstand the inhibition mechanism of the cephalosporins, we carried out molecular dockingstudies with Glide docking and Induced-fit Docking methods. Binding sites of hGR werepredicted and the best suitable binding site of the drugs was identified with the Glide dockingmethod. 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 forCefoperazone, Cefodizime, and Ceftazidime, dimerization site for Cefotaxime, Ceftriaxone,and Cefuroxime, and aromate binding site for Ceftizoxime. The Binding affinity of theCefoperazone was calculated as -10.643 kcal/mol. The results have indicated that hGR enzymewould be inhibited with different mechanisms because of its several druggable sites. Thesefindings would be helpful for designing new inhibitors for hGR enzyme and understanding ofpotential inhibition mechanism of its other known inhibitors.