Design, Synthesis and In Vitro Evaluation of Levodopa Stearic Acid Hydrazide Conjugate for the Management of Parkinson's DiseaseNovel Conjugate for Parkinson's Disease

Drug Res (Stuttg). 2024 Feb;74(2):60-66. doi: 10.1055/a-2234-9859. Epub 2024 Jan 29.

Abstract

Parkinson's disease is the highest prevalent neurodegenerative disease in elderly individuals after Alzheimer's disease. The pathological identification for Parkinson's disease is loss of dopaminergic neurons in substantia nigra region of the brain that in turn leads to dopamine deficiency that affects the body's normal physiological and neurological disorder. The important drawback in the modality of treatment is levodopa is only supplying depleted dopamine in the brain, it does not affect neurodegeneration. Even though levodopa manages the disease, an alternative treatment strategy is required to stop or prevent further degeneration of neuron. The compound with neuroprotector activity suits the requirement. Of them, stearic acid plays a vital role in protecting neurons against oxidative stress through a Phosphoinositide 3-kinase-dependent mechanism. Hence, our present study aimed to design, synthesize, and characterize the levodopa stearic acid hydrazide conjugate. Additionally, evaluate the cytotoxicity of synthesized compound in SHSY5Y: cell lines. In brief, levodopa was conjugated to the stearic acid successfully and was confirmed with Fourier-transform infrared spectroscopy, Nuclear magnetic resonance, and Mass Spectroscopy. In vitro cell viability study in SHSY5Y: cell lines showed elevated cell viability in 0.134 µm concentration of Conjugate, and 0.563 µm concentration of levodopa. Showing that the synthesized compound could offer an improved treatment strategy for Parkinson's disease.

MeSH terms

  • Aged
  • Antiparkinson Agents / metabolism
  • Antiparkinson Agents / pharmacology
  • Antiparkinson Agents / therapeutic use
  • Dopamine / metabolism
  • Dopaminergic Neurons
  • Humans
  • Levodopa / metabolism
  • Levodopa / pharmacology
  • Neurodegenerative Diseases*
  • Parkinson Disease* / drug therapy
  • Parkinson Disease* / pathology
  • Phosphatidylinositol 3-Kinases / metabolism
  • Stearic Acids*

Substances

  • Levodopa
  • stearic acid
  • Dopamine
  • Phosphatidylinositol 3-Kinases
  • Antiparkinson Agents
  • Stearic Acids