Cyanoacetohydrazide linked to 1,2,3-triazole derivatives: a new class of α-glucosidase inhibitors

In this work, a novel series of cyanoacetohydrazide linked to 1,2,3-triazoles (9a-n) were designed and synthesized to be evaluated for their anti-alpha-glucosidase activity, focusing on the fact that alpha-glucosidase inhibitors have played a significant role in the management of type 2 diabetes mellitus. All synthesized compounds except 9a exhibited excellent inhibitory potential, with IC50 values ranging from 1.00 +/- 0.01 to 271.17 +/- 0.30 mu M when compared to the standard drug acarbose (IC50 = 754.1 +/- 0.5 mu M). The kinetic binding study indicated that the most active derivatives 9b (IC50 = 1.50 +/- 0.01 mu M) and 9e (IC50 = 1.00 +/- 0.01 mu M) behaved as the uncompetitive inhibitors of alpha-glucosidase with K-i = 0.43 and 0.24 mu M, respectively. Moreover, fluorescence measurements were conducted to show conformational changes of the enzyme after binding of the most potent inhibitor (9e). Calculation of standard enthalpy (Delta H-m degrees) and entropy (Delta S-m degrees) values confirmed the construction of hydrophobic interactions between 9e and the enzyme. Also, docking studies indicated desired interactions with important residues of the enzyme which rationalized the in vitro results.

Automated summary

A series of newly designed and synthesized cyanoacetohydrazide linked to 1,2,3-triazoles compounds were evaluated for their anti-alpha-glucosidase activity. Most of the synthesized compounds showed excellent inhibitory potential, with 9b and 9e exhibiting the highest activity. Kinetic binding studies and fluorescence measurements confirmed the interaction between these compounds and the enzyme.