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

Sompong Sansenya , Chankan Winyakul, Kesinee Nanok, Waya S. Phutdhawong


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 a-glucosidase and a-amylase and free radical scavenging activity. The structures of                  4a and 4b were determined through spectral studies (1H-NMR).

Findings / Results: Both compounds 4a and 4b had highest inhibitory potential on a-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 a-glucosidase and a-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 a-glucosidase and a-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 a-glucosidase and a-amylase, and their free radical scavenging properties might be applied to the therapeutic care of patients with type 2 diabetes mellitus.


-Glucosidase and -amylase inhibitory activity; Diabetes type 2; Type 2 diabetes mellitus, N-acetylpyrrolidine.

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