Novel metal complexes containing 6-methylpyridine-2-carboxylic acid as potent ?-glucosidase inhibitor: synthesis, crystal structures, DFT calculations, and molecular docking

Abstract

Abstract: The World Health Organization (WHO) report shows that diabetes mellitus (DM) will be one of the ten deadly diseases in the near future. The best way to prevent DM is to decrease blood glucose levels and keep under control; therefore, it is important to design and synthesize the effective inhibitors that can be used in the treatment of DM disease. In this respect, a series of ten metal complexes containing 6-methylpyridine-2-carboxylic acid {[Cr(6-mpa)2(H2O)2]·H2O·NO3, (1), [Mn(6-mpa)2(H2O)2], (2), [Ni(6-mpa)2(H2O)2]·2H2O, (3), [Hg(6-mpa)2(H2O)], (4), [Cu(6-mpa)2(Py)], (5), [Cu(6-mpa)2(H2O)]·H2O, (6), [Zn(6-mpa)2(H2O)]·H2O, (7), [Fe(6-mpa)3], (8), [Cd(6-mpa)2(H2O)2]·2H2O, (9), and [Co(6-mpa)2(H2O)2]·2H2O, (10)} were synthesized as ?-glucosidase inhibitors. We found that the IC50 values of the synthesized complexes ranged from 0.247 ± 0.10 to > 600 ?M against ?-glucosidase. The spectral analyses for these complexes characterized by XRD and LC–MS/MS were also carried out by FT-IR and UV–Vis spectra. Additionally, the DFT/HSEh1PBE/6-311G(d,p)/LanL2DZ level was applied to obtain optimal molecular geometries and spectral behaviors as well as significant contributions to the electronic transitions for the complexes. The molecular docking study was also performed to display interactions between the target protein (the template structure Saccharomyces cerevisiae isomaltase) and the synthesized complexes (1–10). Graphic abstract: [Figure not available: see fulltext.]. © 2020, Springer Nature Switzerland AG.