Design and synthesis of garlic-related unsymmetrical thiosulfonates as potential Alzheimer's disease therapeutics: In vitro and in silico study

Bioorg Med Chem. 2021 Jun 15:40:116194. doi: 10.1016/j.bmc.2021.116194. Epub 2021 May 1.

Abstract

Garlic contains a wide range of organosulfur compounds, which exhibit a broad spectrum of biological activities. Amongst the sulfur-containing compounds in garlic, the thiosulfonates are considerably popular in various fields. In light of this, we decided to investigate the enzyme inhibition ability of thiosulfonates. In this paper, the synthesis and biological activity of a small library of unsymmetrical thiosulfonates as inhibitors of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) are described. The activity evaluation revealed nanomolar IC50 and Ki values against both enzymes tested. Furthermore, molecular docking studies allowed for the determination of possible binding interactions between the thiosulfonates and AChE.

Keywords: Acetylcholinesterase; Butyrylcholinesterase; Enzyme inhibition; Garlic; Organosulfur compounds; Thiosulfonate.

MeSH terms

  • Acetylcholinesterase / metabolism
  • Alzheimer Disease / drug therapy*
  • Alzheimer Disease / metabolism
  • Butyrylcholinesterase / metabolism
  • Cholinesterase Inhibitors / chemical synthesis
  • Cholinesterase Inhibitors / chemistry
  • Cholinesterase Inhibitors / pharmacology*
  • Dose-Response Relationship, Drug
  • Drug Design*
  • Garlic / chemistry*
  • Humans
  • Molecular Docking Simulation
  • Molecular Structure
  • Neuroprotective Agents / chemical synthesis
  • Neuroprotective Agents / chemistry
  • Neuroprotective Agents / pharmacology*
  • Structure-Activity Relationship
  • Thiosulfonic Acids / chemical synthesis
  • Thiosulfonic Acids / chemistry
  • Thiosulfonic Acids / pharmacology*

Substances

  • Cholinesterase Inhibitors
  • Neuroprotective Agents
  • Thiosulfonic Acids
  • Acetylcholinesterase
  • Butyrylcholinesterase