Molecular Neurobiology

, Volume 56, Issue 2, pp 1221–1232 | Cite as

(E)-Nicotinaldehyde O-Cinnamyloxime, a Nicotine Analog, Attenuates Neuronal Cells Death Against Rotenone-Induced Neurotoxicity

  • Juan Camilo Jurado-Coronel
  • Alix E. Loaiza
  • John E. Díaz
  • Ricardo Cabezas
  • Ghulam Md Ashraf
  • Amirhossein Sahebkar
  • Valentina Echeverria
  • Janneth GonzálezEmail author
  • George E. BarretoEmail author


Parkinson’s disease (PD) is a neurodegenerative pathology characterized by resting tremor, rigidity, bradykinesia, and loss of dopamine-producing neurons in the pars compacta of the substantia nigra in the central nervous system (CNS) that result in dopamine depletion in the striatum. Oxidative stress has been documented as a key pathological mechanism for PD. Epidemiological studies have shown that smokers have a lower incidence of PD. In this aspect, different studies have shown that nicotine, a chemical compound found in cigarette, is capable of exerting beneficial effects in PD patients, but it can hardly be used as a therapeutic agent because of its inherent toxicity. Several studies have suggested that the use of nicotine analogs can have the same benefits as nicotine but lack its toxicity. In this study, we assessed the effects of two nicotine analogs, (E)-nicotinaldehyde O-cinnamyloxime and 3-(pyridin-3-yl)-3a,4,5,6,7,7a-hexahidrobenzo[d]isoxazole, in an in vitro model of PD. Initially, we performed a computational prediction of the molecular interactions between the nicotine analogs with the α7 nicotinic acetylcholine receptor (nAChR). Furthermore, we evaluated the effect of nicotine, nicotine analogs and rotenone on cell viability and reactive oxygen species (ROS) production in the SH-SY5Y neuronal cell line to validate possible protective effects. We observed that pre-treatment with nicotine or (E)-nicotinaldehyde O-cinnamyloxime (10 μM) improved cell viability and diminished ROS production in SH-SY5Y cells insulted with rotenone. These findings suggest that nicotine analogs have a potential protective effect against oxidative damage in brain pathologies.


Parkinson’s disease Nicotine analogs (E)-nicotinaldehyde O-cinnamyloxime Rotenone Cell viability Oxidative stress 



This work was supported by Pontificia Universidad Javeriana (PUJ grants # 6337 and 6701) to GEB.

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest.

Supplementary material

12035_2018_1163_MOESM1_ESM.docx (2.8 mb)
ESM 1 (DOCX 2895 kb)


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© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Departamento de Nutrición y Bioquímica, Facultad de CienciasPontificia Universidad JaverianaBogotáColombia
  2. 2.Departamento de Química, Facultad de CienciasPontificia Universidad JaverianaBogotáColombia
  3. 3.King Fahd Medical Research CenterKing Abdulaziz UniversityJeddahSaudi Arabia
  4. 4.Neurogenic Inflammation Research CenterMashhad University of Medical SciencesMashhadIran
  5. 5.Biotechnology Research Center, Pharmaceutical Technology InstituteMashhad University of Medical SciencesMashhadIran
  6. 6.School of PharmacyMashhad University of Medical SciencesMashhadIran
  7. 7.Facultad de Ciencias de la SaludUniversidad San SebastiánConcepciónChile
  8. 8.Bay Pines VA Healthcare System, Research and Development, Bay Pines VAHCSBay PinesUSA

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