Cobalt(II), nickel(II), copper(II) and zinc(II) complexes of thiadiazole based Schiff base ligands: Synthesis, structural characterization, DFT, antidiabetic and molecular docking studies

Abstract

A new series of transition metal complexes of type [M(L1-3)(H2O)(CH3COO)] where, M = Co(II), Ni(II), Cu(II) & Zn(II), and L1 = 2-(((1,3,4-thiadiazol-2-yl)imino)methyl)-6-ethoxyphenol; L2 = 2-ethoxy-6-(((5-methyl-1,3,4-thiadiazol-2-yl)imino)methyl)phenol; L3 = 2-ethoxy-6-(((5-(trifluoromethyl)-1,3,4-thiadiazol-2-yl)imino)methyl)phenol; were synthesized and characterized by various spectral and physico-analytical techniques such as 1H, 13CNMR , FTIR, HRMS, XRD, ESR, TGA, SEM and EDAX. The studies envisaged a penta-coordinated geometry for the complexes, where the Schiff base ligands act in a tridentate manner via the azomethine nitrogen, deprotonated oxygen and one of the nitrogen atom of thiadiazole heterocycle. DFT/B3LYP theoretical method was utilised for calculations of molecular electrostatic potential, HUMO-LUMO energy values of selected compounds. In an in-vitro experiment, the antidiabetic effects of the synthesized compounds were assessed on α-amylase and α-glucosidase enzymes. It was found that compounds 14 and 15 revealed good biological potency with IC50 value close to Acarbose (standard). In-silico study of the synthesized compounds was carried out to check the drug-likeness and it was observed that compounds can be used as orally active drugs. Additionally, molecular docking studies of the potent compounds i.e. 14 and 15, were carried out in the active site of human pancreatic α-amylase (PDB code: 1BSI) and α-glucosidase (PDB code: 5ZCC).