Synthesis and inhibitory activity of N-acetylpyrrolidine derivatives on α-glucosidase and α-amylase

BACKGROUND AND PURPOSE: Carbohydrate hydrolysis enzymes including α-glucosidase and α-amylase are related to type 2 diabetes mellitus. The inhibiting of these enzymes might use for type 2 diabetes mellitus treatment. EXPERIMENTAL APPROACH: N-substituted-acetylpyrrolidine linked with -benzyl- (N-(benzyl)-2-acetylpyrrolidine (4a)) and -tosyl- (N-(tosyl)-2-acetylpyrrolidine (4b)) were synthesized and evaluated for their pharmaceutical properties against α-glucosidase and α-amylase and free radical scavenging activity. The structures of 4a and 4b were determined through spectral studies ((1)H-NMR). FINDINGS / RESULTS: Both compounds 4a and 4b had highest inhibitory potential on α-glucosidase with the IC50 values of 0.52 ± 0.02 and 1.64 ± 0.08 mM, respectively. The kinetic investigation of 4a and 4b against α-glucosidase and α-amylase were functioned in mixed type inhibition. Moreover, both compounds are more likely to bind with the free enzyme than the enzyme-substrate complex based on the Ki < Ki´ on the α-glucosidase and α-amylase enzymes. Regarding the free radical scavenging, 4a had a higher capacity than 4b with IC50 values of 1.01 ± 0.010 mM for 4a and 1.82 ± 0.048 mM for 4b. CONCLUSION AND IMPLICATIONS: Our results indicated that a derivative of N-substitute-acetylpyrrolidine had high potential to inhibit α-glucosidase and α-amylase, and their free radical scavenging properties might be applied to the therapeutic care of patients with type 2 diabetes mellitus.