One-pot multi-component synthesis of novel chromeno[4,3-b]pyrrol-3-yl derivatives as alpha-glucosidase inhibitors

A green and efficient one-pot multi-component protocol was developed for the synthesis of some novel dihydrochromeno[4,3-b]pyrrol-3-yl derivatives through the reaction of arylglyoxals, malono derivatives, and different 4-amino coumarins in ethanol at reflux condition. In this method, all products were obtained in good to excellent yield. Next, all synthesized derivatives were evaluated for their alpha-glucosidase inhibitory activity. Most of the compounds displayed potent inhibitory activities with IC50 values in the range of 48.65 +/- 0.01-733.83 +/- 0.10 mu M compared to the standard inhibitor acarbose (IC50 = 750.90 +/- 0.14 mu M). The kinetic study of compound 5e as the most potent derivative (IC50 = 48.65 +/- 0.01 mu M) showed a competitive mechanism with a K-i value of 42.6 mu M. Moreover, docking studies revealed that dihydrochromeno[4,3-b]pyrrol-3-yl effectively interacted with important residues in the active site of alpha-glucosidase.