Meldrum-Based-1H-1,2,3-Triazoles as Antidiabetic Agents: Synthesis, In Vitro α-Glucosidase Inhibition Activity, Molecular Docking Studies, and In Silico Approach

Abstract

A series of novel alkyl derivatives (2−5a,b) and 1H-1,2,3-triazole analogues (7a−k) of Meldrum's acid were synthesized in a highly effective way by using "click" chemistry and screened for in vitro α-glucosidase inhibitory activity to examine their antidiabetic potential. 1 H NMR, 13 C-NMR, and highresolution electrospray ionization mass spectra (HR-ESI-MS) were used to analyze each of the newly synthesized compounds. Interestingly, these compounds demonstrated high to moderate αglucosidase inhibitory potency having an IC 50 range of 4.63−80.21 μM. Among these derivatives, compound 7i showed extraordinary inhibitory activity and was discovered to be several times more potent than the parent compound Meldrum (1) and the standard drug acarbose. Later, molecular docking was performed to understand the binding mode and the binding strength of all the compounds with the target enzyme, which revealed that all compounds are well fitted in the active site of α-glucosidase. To further ascertain the structure of compounds, suitable X-ray single crystals of compounds 5a, 7a, and 7h were developed and studied. The current investigation has shown that combining 1H-1,2,3-triazole with the Meldrum moiety is beneficial. Furthermore, this is the first time that the aforementioned activity of these compounds has been reported.

Synthesis, Structural Elucidation, In Silico and In Vitro Studies of New Class of Methylenedioxyphenyl-Based Amide Derivatives as Potential Myeloperoxidase Inhibitors for Cardiovascular Protection

“…α-Glucosidase (α-GD), dipeptidyl peptidase-4 (DPP-4), and myeloperoxidase (MPO) proteins are used for molecular docking. The development of CVD, including atherosclerosis (MPO) 27 and type 2 diabetes (DPP-4 28 and α-GD 29 ), is related to these three proteins (MPO, DPP-4, and α-GD). When a macrophage cell dies due to neutrophil extracellular trap (NETosis) activation, chromatin is released into the extracellular environment to trap and eliminate microorganisms.…”

Synthesis of the chromone‐thiosemicarbazone scaffold as promising α‐glucosidase inhibitors: An in vitro and in silico approach toward antidiabetic drug design

“…[4] The startling surge in cases indicates a global healthcare urgency due to the ineffective containment of this disease by existing clinical interventions. [5] Amidst the increasing prevalence and complications of diabetes, the ongoing challenge is to discover treatments that are both effective and well-tolerated.…”