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

Abstract

A series of novel alkyl derivatives (<b>2-5a,b</b>) and 1<i>H</i>-1,2,3-triazole analogues (<b>7a-k</b>) of Meldrum's acid were synthesized in a highly effective way by using <i>"click"</i> chemistry and screened for in vitro <i>α</i>-glucosidase inhibitory activity to examine their antidiabetic potential. ¹H NMR, ¹³C-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 α-glucosidase inhibitory potency having an IC₅₀ range of 4.63-80.21 μM. Among these derivatives, compound <b>7i</b> showed extraordinary inhibitory activity and was discovered to be several times more potent than the parent compound Meldrum (<b>1</b>) 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 <i>α</i>-glucosidase. To further ascertain the structure of compounds, suitable X-ray single crystals of compounds <b>5a</b>, <b>7a</b>, and <b>7h</b> were developed and studied. The current investigation has shown that combining 1<i>H</i>-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.