Design, synthesis and molecular docking study of novel pyrrole-based α-amylase and α-glucosidase inhibitors

Abstract

In an effort to design and synthesize a new class of α-glucosidase and α-amylase inhibitors, we have synthesized novel pyrrole based molecules using molecular hybridization approach. These novel analogs were synthesized by the novel methodology developed in our lab which comprises of the multi-component direct synthesis route using hypervalent iodine reagent. The compounds were characterized by infrared, 1H nuclear magnetic resonance (NMR), 13C NMR and Mass Spectroscopy. These compounds were screened for their α-amylase and α- glucosidase activity. They showed a varying degree of inhibition with IC50 values ranging between 0.4 to 4.14 µmol/mL and 0.8 to 4.14 µmol/mL for α-amylase and α-glucosidase respectively. Compounds 3, 7, 12, and 18 showed excellent activity as compared to standard acarbose. This has identified a new class of α-amylase and α-glucosidase inhibitor which can be further developed as antihyperglycemic agents. The molecular docking analysis was carried out to better understand of interaction between α-amylase and α-glucosidase target and inhibitors in this series. We also generated a homology model for human α-glucosidase enzyme and identified the key residues at the binding site. The outcome of the study could be used for the rational design of potent and selective α-amylase and α-glucosidase inhibitors, respectively.