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.

Synthesis and Pharmacological Properties of the Benzimidazole Scaffold: A Patent Review

“…These studies revealed that the compound effectively occupied strategic positions within the binding center of HPA, with calculated energies of −8.8 kcal/mol −1 . These findings not only validate the potential of compound 46 as a valuable antidiabetic agent but also provide valuable insights into its mode of action, which could be leveraged for further drug development and optimization [76] …”

“…These findings not only validate the potential of compound 46 as a valuable antidiabetic agent but also provide valuable insights into its mode of action, which could be leveraged for further drug development and optimization. [76] In an endeavor led by Khan and colleagues, the primary objective was the development of a novel class of compounds characterized by benzimidazole-substituted thiadiazole analogs. These compounds were meticulously designed with the intention of evaluating their potential inhibitory effects against two key enzymes in diabetes management: α-glucosidase and α-amylase.…”

Synthesis, Biological Evaluation, and Molecular Docking of Novel Azolylhydrazonothiazoles as Potential Anticancer Agents

“…After everything was done, the resulting poses were analyzed, and the best ones with the largest scores, reasonable RMSD values, and better ligand–protein target interactions were picked and kept for subsequent studies. It is important to note that the co-crystallized ligand (W19) was redocked at its binding pocket on the prepared Target as part of a program validation phase for the applicable MOE program − (Figure ). By getting a low RMSD value (1.21) between the screened compounds and the redocked co-crystallized ligand ( W19 ), a valid performance was demonstrated.…”

Messagenin–based Chalcones: Synthesis, Modification and Perspectives of Antidiabetic Potency

“…Many modern works are devoted to the search for that kind of compounds. [2,3] Unfortunately, current antidiabetic therapy is based on synthetic drugs that very often have side effect, while terpene use is commonly recognized as safe or non-toxic in most cases. Among the available and potential for medical use pentacyclic triterpenoid betulin is a drug approved for the first time worldwide by the EMA for the European Economic Area in 2016 (EU/1/15/1069/ 001).…”