Synthesis, DFT calculations and molecular docking study of mixed ligand metal complexes containing 4,4 '-dimethyl-2,2 '-bipyridyl as alpha-glucosidase inhibitors

Abstract

Novel mixed ligand metal complexes including 4,4'-dimethyl-2,2'-bipyridyl (dmdpy) and 6-methylpyridine-2-carboxylic acid (6-mpaH) {[VO(6-mpa)(dmdpy)]center dot SO3, (1), [Fe(6-mpa)(dmdpy)(NO3)(2)]center dot NO3, (2), Ni(6-mpa)(dmdpy)Cl-2, (3), [Zn(6-mpa)(dmdpy)Cl-2]center dot H2O, (4), Cd(6-mpa)(2)(dmdpy), (5), [Hg(6-mpa)(dmdpy)(NO3)(2)]center dot H2O, (6)} were synthesized as potential alpha-glucosidase inhibitors. Their structural characterizations, vibrational and electronic spectral behaviours were investigated by elemental analysis, LC-MS/MS, FT-IR and UV-Vis spectroscopic techniques. The inhibitory activities of these complexes against alpha-glucosidase (from Saccharomyces cerevisiae, EC No: 3.2.1.20) were determined. The synthesized complexes 1-6 exhibited alpha-glucosidase inhibitory activity with the IC50 values ranging from 0.4699 to >600 mu M. Besides, density functional theory (DFT) calculations in the mode of hybrid HSEh1PBE method with 6-311G(d,p) and LanL2DZ basis sets for optimal complex geometries were fulfilled to obtain the vibrational frequencies and electronic spectral behaviours as well as substantial contributions to the electronic transitions. Furthermore, the molecular docking study was performed to examine protein-ligand interactions between the synthesized complexes (1-6) and target protein (the template structure S. cerevisiae isomaltase (PDBID: 3A4A)). (c) 2019 Elsevier B.V. All rights reserved.