Regioselective syntheses of 2-oxopyridine carbonitrile derivatives and evaluation for antihyperglycemic and antioxidant potential

Abstract

A library of 2-oxopyridine carbonitriles 1-34 was synthesized by regioselective nucleophilic substitution reactions. In the first step, a one-pot multicomponent reaction yield pyridone intermediates. The resulting pyridone intermediates were then reacted with phenacyl halides in DMF and stirred at 100 degrees C for an hour to afford the desired compounds in good yields. Structures of synthetic molecules were characterized by EI-MS, HREI-MS, H-1 NMR, and C-13 NMR, and all thirty-four (34) compounds were found to be new. All synthetic compounds were examined for antidiabetic and antioxidant potential. The compounds exhibited alpha-glucosidase inhibitory potential in the range of IC50 = 3.00 +/- 0.11-43.35 +/- 0.67 mu M and alpha-amylase inhibition potential in the range of IC50 = 9.20 +/- 0.14-65.56 +/- 1.05 mu M. Among the tested compounds, 1 showed the most significant alpha-glucosidase inhibitory activity, with an IC50 value of 3.00 +/- 0.11 mu M, while the most active compound against alpha-amylase was 6, with an IC50 value = 9.20 +/- 0.14 mu M. The kinetic studies and analysis indicated that the compounds followed the competitive mode of inhibition. In addition, the molecular docking studies showed the interaction profile of all molecules with the binding site residues of alpha-glucosidase and alpha-amylase enzymes.