A gliclazide complex based on palladium towards Alzheimer's disease: promising protective activity against Aβ-induced toxicity in C. elegans

Chem Commun (Camb). 2022 Feb 1;58(10):1514-1517. doi: 10.1039/d1cc04404d.

Abstract

A new palladium coordination compound based on gliclazide with the chemical formula [Pd(glz)2] (where glz = gliclazide) has been synthesized and characterised. The structural characterization reveals that this material consists of mononuclear units formed by a Pd2+ ion coordinated to two molecules of the glz ligand, in which palladium ions exhibit a distorted plane-square coordination sphere. This novel material behaves like a good and selective inhibitor of butyrylcholinesterase, one of the most relevant therapeutic targets against Alzheimer's disease. Analysis of the enzyme kinetics showed a mixed mode of inhibition, the title compound being capable of interacting with both the free enzyme and the enzyme-substrate complex. Finally, the palladium compound shows promising protective activity against Aβ-induced toxicity in the Caenorhabditis elegans model, which has never been reported.

MeSH terms

  • Alzheimer Disease / drug therapy
  • Amyloid beta-Peptides / metabolism
  • Amyloid beta-Peptides / pharmacology
  • Animals
  • Butyrylcholinesterase / chemistry
  • Butyrylcholinesterase / metabolism
  • Caenorhabditis elegans / drug effects*
  • Coordination Complexes / chemistry*
  • Coordination Complexes / metabolism
  • Coordination Complexes / pharmacology
  • Coordination Complexes / therapeutic use
  • Disease Models, Animal
  • Gliclazide / chemistry*
  • Molecular Conformation
  • Palladium / chemistry*
  • Protective Agents / chemistry
  • Protective Agents / metabolism
  • Protective Agents / pharmacology*
  • Protective Agents / therapeutic use

Substances

  • Amyloid beta-Peptides
  • Coordination Complexes
  • Protective Agents
  • Palladium
  • Butyrylcholinesterase
  • Gliclazide