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

ABSTRACT: 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-α-glucosidase activity, focusing on the fact that α-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 μM when compared to the standard drug acarbose (IC₅₀ = 754.1 ± 0.5 μM). The kinetic binding study indicated that the most active derivatives 9b (IC₅₀ = 1.50 ± 0.01 μM) and 9e (IC₅₀ = 1.00 ± 0.01 μM) behaved as the uncompetitive inhibitors of α-glucosidase with K_i = 0.43 and 0.24 μM, 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 (ΔH_m°) and entropy (ΔS_m°) 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.

SUBMITTER: Iraji A 

PROVIDER: S-EPMC9125976 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature