Novel amino acid Schiff base Zn(II) complexes as new therapeutic approaches in diabetes and Alzheimer's disease: Synthesis, characterization, biological evaluation, and molecular docking studies

J Biochem Mol Toxicol. 2022 Mar;36(3):e22969. doi: 10.1002/jbt.22969. Epub 2021 Nov 23.

Abstract

Schiff bases are compounds that have gained importance in the paint industry due to their colorful nature and in the field of chemistry and biochemistry due to their biological activities. Various biological applications of Schiff bases, such as antitumor, antifungal, antibacterial, antioxidant, antituberculosis, and anthelmintic, have been widely studied. Within the scope of the study, 5-bromo-2-hydroxybenzaldehyde and amino acid methyl esters (isoleucine, phenylalanine, and methionine) and amino acid Schiff bases were synthesized first. The synthesis of the new Zn(II) complexes of these Schiff bases was carried out by the reaction of synthesized Schiff bases and Zn(OAc)2 ·2H2 O. The structures of the synthesized complexes were elucidated using elemental analysis, Fourier transform infrared, nuclear magnetic resonance, UV-visible, and thermal analysis spectroscopy techniques. These synthesized salts were found to be effective inhibitor compounds for the α-glycosidase, and acetylcholinesterase enzyme with Ki values in the range of 30.50 ± 3.82-38.17 ± 6.26 µM for α-glycosidase, 3.68 ± 0.54-10.27 ± 1.68 µM for butyrylcholinesterase, and 6.26 ± 0.83-15.73 ± 4.73 µM for acetylcholinesterase, respectively.

Keywords: Zn(II) complexes; amino acid Schiff base; enzyme inhibition; molecular docking.

MeSH terms

  • Acetylcholinesterase* / chemistry
  • Alzheimer Disease / drug therapy*
  • Butyrylcholinesterase / chemistry*
  • Cholinesterase Inhibitors* / chemical synthesis
  • Cholinesterase Inhibitors* / chemistry
  • Cholinesterase Inhibitors* / therapeutic use
  • Coordination Complexes* / chemical synthesis
  • Coordination Complexes* / chemistry
  • Coordination Complexes* / therapeutic use
  • GPI-Linked Proteins / antagonists & inhibitors
  • GPI-Linked Proteins / chemistry
  • Humans
  • Molecular Docking Simulation*
  • Schiff Bases / chemical synthesis
  • Schiff Bases / chemistry
  • Schiff Bases / therapeutic use
  • Zinc* / chemistry
  • Zinc* / therapeutic use

Substances

  • Cholinesterase Inhibitors
  • Coordination Complexes
  • GPI-Linked Proteins
  • Schiff Bases
  • ACHE protein, human
  • Acetylcholinesterase
  • Butyrylcholinesterase
  • Zinc