Molecular docking, molecular dynamics simulations and in vitro screening reveal cefixime and ceftriaxone as GSK3β covalent inhibitors.

ABSTRACT: GSK3β is a serine/threonine kinase that has been suggested as a putative drug target for several diseases. Recent studies have reported the beneficial effects of cephalosporin antibiotics in cancer and Alzheimer's disease, implying potential inhibition of GSK3β. To investigate this mechanism, four cephalosporins, namely, cefixime, ceftriaxone, cephalexin and cefadroxil were docked into the GSK3β binding pocket. The third-generation cephalosporins, cefixime and ceftriaxone, exhibited the best docking scores due to the exclusive hydrogen bonding between their aminothiazole group and hinge residues of GSK3β. The stability of top-ranked poses and the possibility of covalent bond formation between the carbonyl carbon of the β-lactam ring and the nucleophilic thiol of Cys-199 were evaluated by m

SUBMITTER: Nassar H 

PROVIDER: S-EPMC10087387 | biostudies-literature | 2023 Apr

REPOSITORIES: biostudies-literature