Cu(II) complexes based on benzotriazole: structure-function relationship, synthesis, crystal structure and antidiabetic activity

This study investigates the relationship between the structure of copper(II) complexes and antidiabetic activity. Six Cu (II) metal complexes were synthesized using 1-[(3,5-dimethyl-1-H-triazole-1-yl)methyl]-1H-benzotriazole (dmbt), 1-[(2-ethyl-4-methylimidazole-1-yl) methyl] − 1H-benzotriazole (emimb), and 1-[(2-ethyl-1H-benzimidazole-1-yl) methyl]-1H-benzotriazole (ebmb) as ligands, and their antidiabetic activity was evaluated. The X-ray single crystal diffraction results show that complexes 1 and 5 have a mononuclear structure, while complexes 2, 3, 4, and 6 have a binuclear structure. We evaluated the antidiabetic activity of six complexes, and the results of α-amylase and α-glucosidase inhibition experiments showed that complexes 2, 4, and 6 had high inhibitory activity, with IC50 values of 0.892 ± 0.085 mM, 0.551 ± 0.049 mM, and 1.447 ± 0.069 mM for α-amylase, respectively; the IC50 values for α-glucosidase were 4.05 ± 0.06 μM, 0.17 ± 0.22 μM, and 3.59 ± 0.01 μM, respectively. Furthermore, in experiments assessing their effect on glucose consumption in HepG2 cells with insulin resistance (IR), complexes 2, 4, and 6 moderately improved glucose consumption in IR-HepG2 cells, representing 1.15-fold, 1.09-fold, and 1.2-fold increases compared to the model group, respectively. Six Cu(II) complexes based on benzotriazole-derived ligands were synthesized. Antidiabetic activity was evaluated, and complexes 2, 4, and 6 showed high inhibitory activity against α-amylase and α-glucosidase and moderately improved glucose consumption in IR-HepG2 cells, highlighting the structure-function relationship of these Cu(II) complexes in antidiabetic effects.