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

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 effectiveway by using "click" chemistry andscreened for in vitro & alpha;-glucosidase inhibitoryactivity to examine their antidiabetic potential. H-1 NMR, C-13-NMR, and high-resolution electrospray ionization mass spectra(HR-ESI-MS) were used to analyze each of the newly synthesized compounds.Interestingly, these compounds demonstrated high to moderate & alpha;-glucosidaseinhibitory potency having an IC50 range of 4.63-80.21 & mu;M. Among these derivatives, compound 7i showedextraordinary inhibitory activity and was discovered to be severaltimes more potent than the parent compound Meldrum (1) and the standard drug acarbose. Later, molecular docking was performedto understand the binding mode and the binding strength of all thecompounds with the target enzyme, which revealed that all compoundsare well fitted in the active site of & alpha;-glucosidase.To further ascertain the structure of compounds, suitable X-ray singlecrystals of compounds 5a, 7a, and 7h were developed and studied. The current investigation hasshown that combining 1H-1,2,3-triazole with the Meldrummoiety is beneficial. Furthermore, this is the first time that theaforementioned activity of these compounds has been reported.