Synthesis, Molecular Docking, and Bioactivity Study of Novel Hybrid Benzimidazole Urea Derivatives: A Promising α-Amylase and α-Glucosidase Inhibitor Candidate with Antioxidant Activity

Abstract

A novel series of benzimidazole ureas 3a–h were elaborated using 2-(1H-benzoimidazol-2-yl) aniline 1 and the appropriate isocyanates 2a–h. The antioxidant and possible antidiabetic activities of the target benzimidazole-ureas 3a–h were evaluated. Almost all compounds 3a–h displayed strong to moderate antioxidant activities. When tested using the three antioxidant techniques, TAC, FRAP, and MCA, compounds 3b and 3c exhibited marked activity. The most active antioxidant compound in this family was compound 3g, which had excellent activity using four different methods: TAC, FRAP, DPPH-SA, and MCA. In vitro antidiabetic assays against α-amylase and α-glucosidase enzymes revealed that the majority of the compounds tested had good to moderate activity. The most favorable results were obtained with compounds 3c, 3e, and 3g, and analysis revealed that compounds 3c (IC50 = 18.65 ± 0.23 μM), 3e (IC50 = 20.7 ± 0.06 μM), and 3g (IC50 = 22.33 ± 0.12 μM) had good α-amylase inhibitory potential comparable to standard acarbose (IC50 = 14.21 ± 0.06 μM). Furthermore, the inhibitory effect of 3c (IC50 = 17.47 ± 0.03 μM), 3e (IC50 = 21.97 ± 0.19 μM), and 3g (IC50 = 23.01 ± 0.12 μM) on α-glucosidase was also comparable to acarbose (IC50 = 15.41 ± 0.32 μM). According to in silico molecular docking studies, compounds 3a–h had considerable affinity for the active sites of human lysosomal acid α-glucosidase (HLAG) and pancreatic α-amylase (HPA), indicating that the majority of the examined compounds had potential anti-hyperglycemic action.