Isatin-based ibuprofen and mefenamic acid Schiff base derivatives as dual inhibitors against urease and α-glucosidase: In vitro, in silico and cytotoxicity studies

alpha-Glucosidase and urease inhibitors have emerged as crucial for developing therapeutic drugs targeting diabetes and gastrointestinal disorders. This study reports on new series of ibuprofen and mefenamic acid Schiff base derivatives incorporating isatin as dual inhibitors of alpha-glucosidase and urease enzymes. These synthesized derivatives (7a-r) were structurally characterized by 1H NMR, 13C NMR and HRMS (EI). Biological evaluation (IC50) identified several derivatives i.e., 7a (urease = 17.37 + 1.37 mu M, alpha-glucosidase = 44.1 + 1.15 mu M), 7j, (urease = 16.61 + 1.37 mu M, alpha-glucosidase = 81.2 + 1.33 mu M), 7o, (urease = 18.63 + 1.27 mu M, alpha-glucosidase = 70.3 + 1.14 mu M), 7r (urease = 11.36 + 1.32 mu M, alpha-glucosidase = 39.3 + 1.17 mu M), as dual inhibitors of urease (thiourea 21.37 + 1.76 mu M) and alpha-glucosidase (acarbose 375.82 + 1.76 mu M) enzymes. These bioactive derivatives were explored for cell viability studies against mononuclear cells revealing a good cytocompatibility. In silico molecular docking studies were also conducted to predict the binding mode of new derivatives with target enzymes that were found consistent with the results of in vitro research.