Polyethylene glycol mediated, novel, one-pot three-component synthesis of benzimidazolyl-thiazoles as potent α-glucosidase inhibitors: Design, synthesis, molecular modelling, ADME studies

•Series of novel thizolyl-benzimidazole derivatives were synthesized using PEG-400 solvent via MCR approach.•These are evaluated for in-vitro anti-diabetic activity screening with Acarbose.•Among the tested compounds, compound 4d, 4c, 4 h, 4j and 4b have shown significant anti-diabetic activity.•The IC50 values 12.02 ± 0.56; 12.25± 0.28; 12.74 ± 0.45; 17.83 ± 0.21 and 19.10 ± 0.88 μg/mL respectively.•Molecular docking studies revealed compounds 4c and 4d to have stable binding patterns to the human pancreatic α–amylase (PDB ID: 4W93) with Trp43, Tyr59, Tyr62, His305, and Asp356 amino acid residues.•In-silico ADME analysis: all compounds follow the Lipinski's rule of 5. Polyethylene glycol promoted, novel, one-pot, three-component synthesis of benzimidazole based thaizole derivatives (4a-s) has been synthesized via a multi-component approach by using 5-amino-2-mercaptobenzimidazole, phenyl isothiocyanates, and substituted phenacyl bromides using PEG-400 as a recyclable and greener solvent in a shorter reaction time without any by-products. All the synthesized compounds (4a-s) were well characterized by analytical and spectroscopic techniques. Furthermore, some of the synthesized compounds were evaluated for their in-vitro α-amylase inhibition activity using Acarbose as a standard positive control. Among the tested scaffolds, compound 4d, 4c, 4 h, 4j and 4b have shown significant inhibitory activity against α-amylase enzyme with IC50 values 12.02 ± 0.56; 12.25± 0.28; 12.74 ± 0.45; 17.83 ± 0.21 and 19.10 ± 0.88 μg/mL respectively. Also we insight in to the molecular docking studies, based on the binding results, compounds 4c and 4d to have shown stable binding patterns to the human pancreatic α–amylase with montbretin A (PDBID: 4W93). The structure-activity relationship (SAR) studies of all the title scaffolds were also established. The α- amylase inhibition, molecular docking studies, molecular dynamic simulations, and drug-likeness properties (Lipinski parameters and in-silico ADME properties) of the title compounds were suggested that these are promising anti-diabetic active skeletons. [Display omitted]