Synthesis, molecular docking, α-glucosidase inhibition, and antioxidant activity studies of novel benzimidazole derivatives

A novel series of N -methyl/benzyl-substituted benzimidazolyl-linked para -substituted benzyl-based compounds containing 2,4-thiazolidinediones, dimethyl malonate (DMM), and diethyl malonate (DEM) 17 – 27 were designed, docked, synthesized, and evaluated for their antidiabetic activity studies. Structures of all the synthesized compounds were confirmed through 1 H NMR, 13 C NMR, FTIR, and mass spectrometry. Four targeted compounds ( 17 – 18 and 22 – 23 ) showed good inhibitory potential in the range of 4.10 ± 0.01 to 9.12 ± 0.06 µM. Furthermore, synthesized compounds 17 – 27 were evaluated for their antioxidant potential and compared with standard ascorbic acid and results showed that compound 18 (EC 50 = 0.176 ± 0.002 mM) being the most active. Compounds 17 – 18 and 22 – 23 exhibited prominent antidiabetic as well as antioxidant activity. Compound 18 was considered a promising candidate for this series. The designed molecules were docked into α-glucosidase protein (PDB Code. 3TOP) to develop a correlation with the α-glucosidase inhibition studies and were also additionally docked into PPARγ proteins (PDB ID: 2PRG) with rosiglitazone (standard drug) to study their PPARγ binding affinity in comparison with rosiglitazone and to classify these compounds for their PPARγ agonistic behavior.