Some metal chelates with Schiff base ligand: synthesis, structure elucidation, thermal behavior, XRD evaluation, antioxidant activity, enzyme inhibition, and molecular docking studies

Abstract

Schiff bases are well-known compounds for having significant biological properties. In this study, a new Schiff base ligand and its metal complexes were synthesized, and their antioxidant and enzyme inhibitory activities were evaluated. The new Schiff base ligand was synthesized with the condensation reaction of 6-tert-butyl 3-ethyl 2-amino-4,5-dihydrothieno[2,3-c]pyridine-3,6(7H)-dicarboxylate and 2-hydroxybenzaldehyde compounds. Fe(II), Co(II), and Ni(II) metal complexes of the novel Schiff base ligand were synthesized and characterized. The purity and molecular formula of the synthesized compounds were identified with elemental analysis, infrared, ultraviolet-visible, mass spectrophotometry, powder XRD, magnetic and thermal measurements. The Schiff base acted as a three dentate chelate. The analytical and spectroscopic data suggested an octahedral geometry for the complexes. The in vitro antioxidant method studies elucidated a more effective antioxidant character of the Schiff base ligand than its metal complexes but a less effective antioxidant potential than the standard antioxidant compounds. The enzyme inhibition potentials of the synthesized compounds for AChE, BChE, and GST enzymes were determined by in vitro enzyme activity methods. The Schiff base ligand was discovered to be the best inhibitor for the AChE and BChE with the values of 7.13 ± 0.84 µM and 5.75 ± 1.03 µM K_i, respectively. Moreover, the Fe(II) complex displayed the best K_i value as 9.37 ± 1.06 µM for the GST enzyme. Finally, molecular docking studies were carried out to see the structural interactions of the compounds. The metal complexes demonstrated better binding affinities with the AChE, BChE, and GST enzymes than the Schiff base ligand. This study identified a potential Schiff base molecule against both AChE and BChE targets to further investigate for in vivo and safety evaluation.

Keywords: Antioxidant activity; Enzyme inhibition; Metal complexes; Molecular docking; Schiff base.