Natural products and their derivatives as multifunctional ligands against Alzheimer's disease

Drug Dev Res. 2020 Apr;81(2):165-183. doi: 10.1002/ddr.21587. Epub 2019 Aug 20.

Abstract

Alzheimer's disease (AD), a complex neurodegenerative disorder causing multiple cellular changes including impaired cholinergic system, beta-amyloid (βA) aggregation, tau hyperphosphorylation, metal dyshomeostasis, neuroinflammation, and many other pathways are involved in the pathogenesis of the disease. However, the exact cause of the disease is not known. Natural products such as flavonoids, alkaloids, resveratrol, and curcumin have multifunctional properties, and have drawn the attention of the researchers because these molecules are capable of interacting concurrently with the multiple targets of AD. Therefore, natural products and their derivatives with proven efficacy could be used in the management of the neurodegenerative disorders. This review focuses on the natural product based multitarget directed ligands like tacrine-coumarin, tacrine-huperzine A, harmine-isoxazoline, berberine-thiophenyl, galantamine-indole, pyridoxine-resveratrol, donepezil-curcumin and their mode of action.

Keywords: Alzheimer's; alkaloid; flavonoid; multitarget ligand.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Alzheimer Disease / drug therapy*
  • Alzheimer Disease / metabolism
  • Biological Products / chemistry
  • Biological Products / pharmacology*
  • Biological Products / therapeutic use
  • Humans
  • Ligands
  • Molecular Targeted Therapy
  • Signal Transduction / drug effects*

Substances

  • Biological Products
  • Ligands