A novel series of mixed-ligand M(II) complexes containing 2,2 '-bipyridyl as potent alpha-glucosidase inhibitor: synthesis, crystal structure, DFT calculations, and molecular docking

摘要

Diabetes mellitus (DM) is a common degenerative disease and characterized by high blood glucose levels. Since the effective antidiabetic treatments attempt to decrease blood glucose levels, keeping glucose under control is very important. Recent studies have demonstrated that alpha-glucosidase inhibitor improves postprandial hyperglycemia and then reduces the risk of developing type 2 diabetes in patients. Therefore, the design and synthesis of high affinity glucosidase inhibitors are of great importance. In this regard, novel series of mixed-ligand M(II) complexes containing 2,2 '-bipyridyl {[Hg(6-mpa)(2)(bpy)(OAc)]center dot 2H(2)O, (1), [Co(6-mpa)(2)(bpy)(2)], (2), [Cu(6-mpa)(bpy)(NO3)]center dot 3H(2)O, (3), [Mn(6-mpa)(bpy)(H2O)(2)], (4), [Ni(6-mpa)(bpy)(H2O)(2)]center dot H2O, (5), [Fe(6-mpa)(bpy)(H2O)(2)]center dot 2H(2)O, (6), [Fe(3-mpa)(bpy)(H2O)(2)]center dot H2O, (7)} were synthesized as potential alpha-glucosidase inhibitors. Their effects on alpha-glucosidase activity were evaluated. All synthesized complexes displayed alpha-glucosidase inhibitory activity with IC50 values ranging from 0.184 +/- 0.015 to > 600 mu M. The experimental spectral analyses were carried out using FT-IR and UV-Vis spectroscopic techniques for these complexes characterized by XRD and LC-MS/MS. Moreover, the calculations at density functional theory approximation were used to obtain optimal molecular geometries, vibrational wavenumbers, electronic spectral behaviors, and major contributions to the electronic transitions for the complexes 1-7. Finally, to display interactions between the synthesized complexes and target protein (the template structure Saccharomyces cerevisiae isomaltase), the molecular docking study was carried out.