Discovery of small-molecule compounds and natural products against Parkinson's disease: Pathological mechanism and structural modification

Eur J Med Chem. 2022 Jul 5:237:114378. doi: 10.1016/j.ejmech.2022.114378. Epub 2022 Apr 18.

Abstract

Parkinson's disease (PD) is the second common neurodegenerative disease characterized by movement disorder. The symptoms of PD harm both the physical and mental health of patients. However, the current treatment strategies for PD only alleviate the symptoms but cannot recover the degenerative process of dopaminergic neurons. Therefore, it is necessary to develop novel and safe drugs for the treatment of PD. In this review, we comprehensively summarized the detailed pathological mechanisms and potential drugable targets of PD. The approved anti-PD drugs in clinical use and the drug candidates under clinical trials were also listed. More importantly, the compounds in the drug discovery phase with in vivo anti-PD activities in the recent two decades (2000-2020) were summarized. The structure-activity relationships (SARs) were also analyzed. Additionally, we predicted all the reviewed compounds' blood-brain barrier (BBB) permeability and statistically analyzed their pharmacological targets and in vivo anti-PD testing models. It is hoped that this review can provide practical information for researchers in the field of anti-PD drug discovery and promote their research work.

Keywords: Drug discovery; Natural products; Parkinson's disease (PD); Small-molecule compounds; Structural modification.

Publication types

  • Review

MeSH terms

  • Biological Products* / pharmacology
  • Biological Products* / therapeutic use
  • Blood-Brain Barrier
  • Dopaminergic Neurons
  • Humans
  • Neurodegenerative Diseases* / pathology
  • Parkinson Disease* / drug therapy
  • Parkinson Disease* / pathology

Substances

  • Biological Products