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

Abstract

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 α-glucosidase inhibitory activity. Most of the compounds displayed potent inhibitory activities with IC ₅₀ values in the range of 48.65 ± 0.01–733.83 ± 0.10 μM compared to the standard inhibitor acarbose (IC ₅₀ = 750.90 ± 0.14 μM). The kinetic study of compound 5e as the most potent derivative (IC ₅₀ = 48.65 ± 0.01 μM) showed a competitive mechanism with a K _i value of 42.6 µM. Moreover, docking studies revealed that dihydrochromeno[4,3-b]pyrrol-3-yl effectively interacted with important residues in the active site of α-glucosidase.

Supplementary Information

The online version contains supplementary material available at 10.1007/s11030-021-10337-w.