Synthesis and Antioxidant Properties of Novel Memantine Derivatives

Cent Nerv Syst Agents Med Chem. 2017;17(2):123-128. doi: 10.2174/1871524916666160625123621.


Background: Medicinal chemistry methodologies are presently used to develop multifunctional molecules which simultaneously reduce oxidative stress, excitotoxicity, metal dyshomeostasis, and neuroinflammation that characterize neuropathological conditions, such as Alzheimer's Disease.

Results: Memantine (MEM) derivatives 1-6 were designed and synthesized as novel multifunctional entities with antioxidant and neuroprotective capabilities to manage neurodegenerative diseases, such as Alzheimer's Disease. In vitro neuroprotective studies were performed by using astroglial GL15 cell line to assess antioxidant capability of MEM derivatives 1-6.

Conclusion: Our outcomes showed that compounds 1 and 5 (at the concentration of 10 μM), containing as antioxidant portion residues of N-acetyl-Cys-OH and N-acetyl-Cys(Allyl)-OH, respectively, revealed a significant neuroprotective activity against oxidative stress, as assessed by NBT assays.

Keywords: Alzheimer's disease; MEM; NMDA antagonist; S-Allylcysteine; cysteine derivatives; neuroprotective.

MeSH terms

  • Antioxidants / chemical synthesis*
  • Antioxidants / pharmacology*
  • Astrocytes / drug effects*
  • Astrocytes / metabolism
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Cell Survival / physiology
  • Excitatory Amino Acid Antagonists / chemical synthesis
  • Excitatory Amino Acid Antagonists / pharmacology
  • Humans
  • Memantine / chemical synthesis*
  • Memantine / pharmacology*


  • Antioxidants
  • Excitatory Amino Acid Antagonists
  • Memantine