Ternary Cobalt(II), Nickel(II), and Copper(II) complexes containing metformin and ethylenediamine: Synthesis, characterization, thermal, in vitro DNA binding, in silico molecular docking, and in vivo antihyperglycemic studies

Abstract

Three new water soluble ternary metal complexes, [Co(metf)(en)2]Cl2(1), [Ni(metf)(en)2]Cl2(2), and [Cu(metf)(en)2]Cl2(3), (Metf = metformin, en = ethylenediamine), were synthesized and characterized, and pharmacodynamic evaluation was reported. From the spectral analysis, octahedral geometry was proposed to all the three metal complexes. The Kinetic parameters have been determined by thermogravimetric data using Coats‐Redfern method. The stability of the complexes was obtained from their molecular orbital structures from which the quantum chemical parameters were calculated using the highest occupied molecular orbital (HOMO)‐lowest unoccupied molecular orbital (LUMO) energies. The DNA binding studies of these complexes were explored by absorption, emission, and viscosity. Groove mode of surface binding of these complexes with DNA was explained by viscosity studies. Nuclease activity exhibited by these complexes on pUC19 DNA was experimented by agarose gel electrophoresis. Discovery Studio 2.1 software was used for docking studies of these complexes into B‐DNA sequence, 5′(D*AP*CP*CP*GP*AP*CP*GP*TP*CP*GP*GP*T)‐3′ retrieved from protein data bank (PDB ID: 423D). The maximum score is seen for complex 1. The antihyperglycemic activity of these complexes was studied in streptozotocin (STZ)‐diabetic rats. The substantial increase in the antihyperglycemic activity of the complexes is seen when compared with pure drug. The maximum antihyperglycemic activity is recorded for complex 1.