Discovery of New Boswellic Acid Hybrid 1-1,2,3-Triazoles for Diabetic Management: In Vitro and In Silico Studies.

A series of 24 new 1-1,2,3-triazole hybrids of 3--acetyl-11-keto-β-boswellic acid (β-AKBA ()) and 11-keto-β-boswellic acid (β-KBA ()) was designed and synthesized by employing "click" chemistry in a highly efficient manner. The 1,3-dipolar cycloaddition reaction between β-AKBA-propargyl ester intermediate or β-KBA-propargyl ester intermediate with substituted aromatic azides in the presence of copper iodide (CuI) and Hünig's base furnished the desired products-1-1,2,3-triazole hybrids of β-AKBA () and β-KBA ()-in high yields. All new synthesized compounds were characterized by H-, C-NMR spectroscopy, and HR-ESI-MS spectrometry. Furthermore, their α-glucosidase-inhibitory activity was evaluated in vitro. Interestingly, the results obtained from the α-glucosidase-inhibitory assay revealed that all the synthesized derivatives are highly potent inhibitors, with IC values ranging from 0.22 to 5.32 µM. Among all the compounds, , , , , , , , , and exhibited exceptional inhibitory potency and were found to be several times more potent than the parent compounds and , as well as standard acarbose. Kinetic studies of compounds and exhibited competitive and mixed types of inhibition, with ki values of 0.84 ± 0.007 and 1.18 ± 0.0012 µM, respectively. Molecular docking was carried out to investigate the binding modes of these compounds with α-glucosidase. The molecular docking interactions indicated that that all compounds are well fitted in the active site of α-glucosidase, where His280, Gln279, Asp215, His351, Arg442, and Arg315 mainly stabilize the binding of these compounds. The current study demonstrates the usefulness of incorporating a 1-1,2,3-triazole moiety into the medicinally fascinating boswellic acids skeleton.