Drug Res (Stuttg) 2024; 74(02): 60-66
DOI: 10.1055/a-2234-9859
Original Article

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

Vasanthi Chinraj
1   Department of Pharmaceutics, JSS College of Pharmacy, JSS Academy of Higher Education & Research, Ooty, Nilgiris, Tamil Nadu, India
Ramakkamma Aishwarya Reddy
2   Department of Pharmaceutics, JSS College of Pharmacy, JSS Academy of Higher Education & Research, Ooty, Nilgiris, Tamil Nadu, India
Jubie Selvaraj
3   Department of Pharmaceutical Chemistry, JSS College of Pharmacy, JSS Academy of Higher Education & Research, Ooty, Nilgiris, Tamil Nadu, India
Raman Sureshkumar
1   Department of Pharmaceutics, JSS College of Pharmacy, JSS Academy of Higher Education & Research, Ooty, Nilgiris, Tamil Nadu, India
› Author Affiliations


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.

Publication History

Received: 01 December 2023

Accepted: 11 December 2023

Article published online:
29 January 2024

© 2024. Thieme. All rights reserved.

Georg Thieme Verlag
Rüdigerstraße 14, 70469 Stuttgart, Germany

  • References

  • 1 Bhat S, Acharya UR, Hagiwara Y. Parkinson’s disease: Cause factors, measurable indicators, and early diagnosis. Computers in Biology and Medicine 2018; 102: 234-241 DOI: 10.1016/j.compbiomed.2018.09.008.
  • 2 Bhatia KP, Bain P, Bajaj N. Consensus Statement on the classification of tremors. from the task force on tremor of the International Parkinson and Movement Disorder Society. Movement Disorders 2018; 33: 75-87 DOI: 10.1002/mds.27121.
  • 3 Xia R, Mao Z-H. Progression of motor symptoms in Parkinson’s disease. Neurosci Bull 2012; 28: 39-48 DOI: 10.1007/s12264-012-1050-z.
  • 4 Aarsland D, Batzu L, Halliday GM. Parkinson disease-associated cognitive impairment. Nat Rev Dis Primers 2021; 7: 47 DOI: 10.1038/s41572-021-00280-3.
  • 5 Pankratz N, Foroud T. Genetics of Parkinson disease. Genetics in Medicine 2007; 9: 801-811 DOI: 10.1097/GIM.0b013e31815bf97c.
  • 6 Dorsey ER, Elbaz A, Nichols E. Global, regional, and national burden of Parkinson’s disease, 1990–2016: a systematic analysis for the Global Burden of Disease Study 2016. The Lancet Neurology 2018; 17: 939-953 DOI: 10.1016/S1474-4422(18)30295-3.
  • 7 Ou Z, Pan J, Tang S. Global Trends in the Incidence, Prevalence, and Years Lived With Disability of Parkinson’s Disease in 204 Countries/Territories From 1990 to 2019. Front Public Health 2021; 9: 776847 DOI: 10.3389/fpubh.2021.776847.
  • 8 Dorsey ER, Sherer T, Okun MS. The Emerging Evidence of the Parkinson Pandemic. J Parkinsons Dis 8: S3-S8 DOI: 10.3233/JPD-181474.
  • 9 DeMaagd G, Philip A. Part 2: Introduction to the Pharmacotherapy of Parkinson’s Disease. With a Focus on the Use of Dopaminergic Agents. P T 2015; 40: 590-600
  • 10 De Miranda BR, Goldman SM, Miller GW. Preventing Parkinson’s Disease: An Environmental Agenda. J Parkinsons Dis 12: 45-68 DOI: 10.3233/JPD-212922.
  • 11 Poewe W, Antonini A, Zijlmans JC. Levodopa in the treatment of Parkinson’s disease: an old drug still going strong. Clin Interv Aging 2010; 5: 229-238
  • 12 Gandhi KR, Saadabadi A. Levodopa (L-Dopa). In: StatPearls. Treasure Island (FL): StatPearls Publishing; 2023
  • 13 Bastide MF, Meissner WG, Picconi B. Pathophysiology of L-dopa-induced motor and non-motor complications in Parkinson’s disease. Progress in Neurobiology 2015; 132: 96-168 DOI: 10.1016/j.pneurobio.2015.07.002.
  • 14 Alberti C. Drug-induced retroperitoneal fibrosis: short aetiopathogenetic note, from the past times of ergot-derivatives large use to currently applied bio-pharmacology. gchir 2015; DOI: 10.11138/gchir/2015.36.4.187.
  • 15 Di Stefano A, Sozio P, Iannitelli A. New drug delivery strategies for improved Parkinson’s disease therapy. Expert Opinion on Drug Delivery 2009; 6: 389-404 DOI: 10.1517/17425240902870405.
  • 16 Assal F, Spahr L, Hadengue A. Tolcapone and fulminant hepatitis. The Lancet 1998; 352: 958 DOI: 10.1016/S0140-6736(05)61511-5.
  • 17 Riederer P, Laux G. MAO-inhibitors in Parkinson’s Disease. Exp Neurobiol 2011; 20: 1-17 DOI: 10.5607/en.2011.20.1.1.
  • 18 Wang Z, Li G, Tang W. Neuroprotective effects of stearic acid against toxicity of oxygen/glucose deprivation or glutamate on rat cortical or hippocampal slices1. Acta Pharmacologica Sinica 2006; 27: 145-150 DOI: 10.1111/j.1745-7254.2006.00259.x.
  • 19 Meiser J, Weindl D, Hiller K. Complexity of dopamine metabolism. Cell Commun Signal 2013; 11: 34 DOI: 10.1186/1478-811X-11-34.
  • 20 Stansley BJ, Yamamoto BK. l-Dopa and Brain Serotonin System Dysfunction. Toxics 2015; 3: 75-88 DOI: 10.3390/toxics3010075.
  • 21 Vesga-Jiménez DJ, Martin C, Barreto GE. Fatty Acids: An Insight into the Pathogenesis of Neurodegenerative Diseases and Therapeutic Potential. Int J Mol Sci 2022; 23: 2577 DOI: 10.3390/ijms23052577.
  • 22 Kilic E, Kilic Ü, Wang Y. The phosphatidylinositol-3 kinase/Akt pathway mediates VEGF’s neuroprotective activity and induces blood brain barrier permeability after focal cerebral ischemia. FASEB j 2006; 20: 1185-1187 DOI: 10.1096/fj.05-4829fje.
  • 23 Sánchez-Alegría K, Flores-León M, Avila-Muñoz E. PI3K Signaling in Neurons: A Central Node for the Control of Multiple Functions. IJMS 2018; 19: 3725 DOI: 10.3390/ijms19123725.
  • 24 Dehkhoda F, Lee CMM, Medina J. The Growth Hormone Receptor: Mechanism of Receptor Activation, Cell Signaling, and Physiological Aspects. Front Endocrinol (Lausanne) 2018; 9: 35 DOI: 10.3389/fendo.2018.00035.
  • 25 Atlas D. DopAmide: Novel, Water-Soluble, Slow-Release l -dihydroxyphenylalanine ( l -DOPA) Precursor Moderates l -DOPA Conversion to Dopamine and Generates a Sustained Level of Dopamine at Dopaminergic Neurons. CNS Neurosci Ther 2016; 22: 461-467 DOI: 10.1111/cns.12518.
  • 26 Brunner-Guenat M, Carrupt P-A, Lisa G. Esters of L-Dopa: Structure-hydrolysis Relationships and Ability to Induce Circling Behaviour in an Experimental Model of Hemiparkinsonism. Journal of Pharmacy and Pharmacology 2011; 47: 861-869 DOI: 10.1111/j.2042-7158.1995.tb05755.x.
  • 27 Panicker N, Ge P, Dawson VL. The cell biology of Parkinson’s disease. Journal of Cell Biology 2021; 220: e202012095 DOI: 10.1083/jcb.202012095.
  • 28 Falkenburger BH, Saridaki T, Dinter E. Cellular models for Parkinson’s disease. J Neurochem 2016; 139: 121-130 DOI: 10.1111/jnc.13618.