The Medicinal Chemistry of Natural and Semisynthetic Compounds against Parkinson's and Huntington's Diseases

ACS Chem Neurosci. 2017 Nov 15;8(11):2356-2368. doi: 10.1021/acschemneuro.7b00283. Epub 2017 Sep 15.

Abstract

Among the diseases affecting the central nervous system (CNS), neurodegenerations attract the interest of both the clinician and the medicinal chemist. The increasing average age of population, the growing number of patients, and the lack of long-term effective remedies push ahead the quest for novel tools against this class of pathologies. We present a review on the state of the art of the molecules (or combination of molecules) of natural origin that are currently under study against two well-defined pathologies: Parkinson's disease (PD) and Huntington's disease (HD). Nowadays, very few tools are available for preventing or counteracting the progression of such diseases. Two major parameters were considered for the preparation of this review: particular attention was reserved to these research works presenting well-defined molecular mechanisms for the studied compounds, and where available, papers reporting in vivo data were preferred. A literature search for peer-reviewed articles using PubMed, Scopus, and Reaxys databases was performed, exploiting different keywords and logical operators: 91 papers were considered (preferentially published after 2015). The review presents a brief overview on the etiology of the studied neurodegenerations and the current treatments, followed by a detailed discussion of the natural and semisynthetic compounds dividing them in different paragraphs considering their several mechanisms of action.

Keywords: CNS; Dementia; Huntington’s disease; Parkinson’s disease; natural products; semisynthetic compounds.

Publication types

  • Review

MeSH terms

  • Animals
  • Anti-Dyskinesia Agents / chemical synthesis
  • Anti-Dyskinesia Agents / chemistry*
  • Anti-Dyskinesia Agents / economics
  • Anti-Dyskinesia Agents / therapeutic use
  • Antioxidants / pharmacology
  • Antioxidants / therapeutic use
  • Antiparkinson Agents / chemical synthesis
  • Antiparkinson Agents / chemistry
  • Antiparkinson Agents / economics
  • Antiparkinson Agents / therapeutic use
  • Autophagy / drug effects
  • Biological Products / chemistry*
  • Biological Products / economics
  • Biological Products / therapeutic use
  • Dementia / drug therapy
  • Dementia / economics
  • Dementia / epidemiology
  • Dopamine / metabolism
  • Drug Discovery
  • Drug Evaluation, Preclinical
  • Humans
  • Huntington Disease / drug therapy*
  • Huntington Disease / economics
  • Huntington Disease / epidemiology
  • Huntington Disease / physiopathology
  • Microglia / drug effects
  • Mitochondria / drug effects
  • Molecular Targeted Therapy
  • Monoamine Oxidase Inhibitors / therapeutic use
  • Oxidative Stress / drug effects
  • Parkinson Disease / drug therapy*
  • Parkinson Disease / economics
  • Parkinson Disease / epidemiology
  • Parkinson Disease / physiopathology
  • Plant Preparations / pharmacology
  • Plant Preparations / therapeutic use
  • Protein Aggregation, Pathological / drug therapy
  • Signal Transduction / drug effects
  • alpha-Synuclein / antagonists & inhibitors

Substances

  • Anti-Dyskinesia Agents
  • Antioxidants
  • Antiparkinson Agents
  • Biological Products
  • Monoamine Oxidase Inhibitors
  • Plant Preparations
  • alpha-Synuclein
  • Dopamine