Novel benzotriazole-benzimidazole metal complexes: structure-activity relationship, synthesis, characterization, and antidiabetic activity

Abstract

To investigate the relationship between structure and antidiabetic activity, four novel metal complexes [Cu2(ebmb)2Cl4] (1), [Zn2(ebmb)Cl4] (2), [Cu(ebmb)SO4]n (3) and [Cu(mbmb)SO4]n (4) have been synthesized by 1-[(2-ethyl-1H-benzimidazole- 1-yl)methyl]-1H-benzotriazole (ebmb) and 1-[(2-methyl-1H-benzimidazole-1-yl) methyl]-1H-benzotriazole (mbmb), and the antidiabetic activities of them have been evaluated. The X-ray single crystal diffraction analysis reveals that complexes 1-2 are binuclear complexes and isostructural expect the different central metal. Complexes 3-4 possess the same central metal but different ligands, and they have very similar structure and they both possess one-dimensional chain structure. We assessed the in vitro antidiabetic activities of the complexes. The results of the α-amylase and α-glucosidase inhibition assays showed that complexes 1 and 4 possessed strongest inhibitory activities with the IC50 values of 1.29mM±0.04 (1) and 4.69mM±0.43 (4) for α-amylase, 0.75±0.04μM (1) and 1.63±0.11μM (4) for α-glucosidase. Finally, we evaluated the effect of complexes 1 and 4 on the glucose consumption of insulin resistant (IR) HepG2 cells, the results showed that both two complexes can improve the IR state of HepG2 cells, the glucose consumption of complex 1-treated IR-HepG2 cells and complex 4-treated IR-HepG2 cells were 1.3 times and 1.18 times as much as the model group, respectively. What's more, the structure-function relationship of complexes had also been discussed in this paper.