Spiroindolone Analogues as Potential Hypoglycemic with Dual Inhibitory Activity on α-Amylase and α-Glucosidase

Inhibition of alpha-amylase and alpha-glucosidase by specified synthetic compounds during the digestion of starch helps control post-prandial hyperglycemia and could represent a potential therapy for type II diabetes mellitus. A new series of spiroheterocyclic compounds bearing oxindole/benzofuran/pyrrolidine/thiazolidine motifs were synthesized via a 1,3-dipolar cyclo-addition reaction approach. The specific compounds were obtained by reactions of chalcones having a benzo[b]furan scaffold (compounds 2a-f), with a substituted isatin (compounds 3a-c) and heterocyclic amino acids (compounds 4a,b). The target spiroindolone analogues 5a-r were evaluated for their potential inhibitory activities against the enzymes alpha-amylase and alpha-glucosidase. Preliminary results indicated that some of the target compounds exhibit promising alpha-amylase and alpha-glucosidase inhibitory activity. Among the tested spiroindolone analogues, the cycloadduct 5r was found to be the most active (IC50 = 22.61 +/- 0.54 mu M and 14.05 +/- 1.03 mu M) as alpha-amylase and alpha-glucosidase inhibitors, with selectivity indexes of 0.62 and 1.60, respectively. Docking studies were carried out to confirm the binding interaction between the enzyme active site and the spiroindolone analogues.