A novel multi-target strategy to attenuate the progression of Parkinson's disease by diamine hybrid AGE/ALE inhibitor

Future Med Chem. 2021 Dec;13(24):2185-2200. doi: 10.4155/fmc-2021-0217. Epub 2021 Oct 12.

Abstract

Instead of a conventional 'one-drug-one-target approach', this article presents a novel multi-target approach with a concept of trapping simultaneously as many detrimental factors as possible involved in the progression of Parkinson's disease. These factors include reactive carbonyl species, reactive oxygen species, Fe3+/Cu2+ and ortho-quinones (o-quinone), in particular. Different from the known multi-target strategies for Parkinson's disease, it is a sort of 'vacuum cleaning' strategy. The new agent consists of reactive carbonyl species scavenging moiety and reactive oxygen species scavenging and metal chelating moiety linked by a spacer. Provided that the capacity of scavenging o-quinones is demonstrated, this type of agent can further broaden its potential therapeutic profile. In order to support this new hypothetical approach, a number of simple in vitro experiments are proposed.

Keywords: AGE/ALE inhibitor; Parkinson's disease; RCS; ROS; methylglyoxal; ortho-quinone; quinoxaline; α-synuclein.

Publication types

  • Review

MeSH terms

  • Copper / chemistry
  • Copper / pharmacology*
  • Diamines / chemistry
  • Diamines / pharmacology*
  • Ferric Compounds / chemistry
  • Ferric Compounds / pharmacology*
  • Humans
  • Molecular Structure
  • Parkinson Disease / drug therapy*
  • Parkinson Disease / metabolism
  • Parkinson Disease / pathology
  • Quinones / chemistry
  • Quinones / pharmacology*
  • Reactive Oxygen Species / metabolism*

Substances

  • Diamines
  • Ferric Compounds
  • Quinones
  • Reactive Oxygen Species
  • Copper