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Article

Neuroprotective Effect of 1,4-Naphthoquinones in an In Vitro Model of Paraquat and 6-OHDA-Induced Neurotoxicity

1
G.B. Elyakov Pacific Institute of Bioorganic Chemistry, Far-Eastern Branch of the Russian Academy of Science, 690022 Vladivostok, Russia
2
School of Natural Sciences, Far Eastern Federal University, Ajax Bay, Russky Island, 690922 Vladivostok, Russia
3
Department of Biomedical Science and Environmental Biology, Kaohsiung Medical University, Kaohsiung City 80708, Taiwan
*
Author to whom correspondence should be addressed.
Academic Editor: Toshio Ohshima
Int. J. Mol. Sci. 2021, 22(18), 9933; https://doi.org/10.3390/ijms22189933
Received: 31 August 2021 / Revised: 10 September 2021 / Accepted: 10 September 2021 / Published: 14 September 2021
Targeted screening using the MTT cell viability test with a mini-library of natural and synthetic 1,4-naphthoquinones and their derivatives was performed in order to increase the survival of Neuro-2a neuroblastoma cells in in vitro paraquat and 6-hydroxydopamine models of Parkinson’s disease. As a result, 10 compounds were selected that could protect neuronal cells from the cytotoxic effects of both paraquat and 6-hydroxydopamine. The five most active compounds at low concentrations were found to significantly protect the activity of nonspecific esterase from the inhibitory effects of neurotoxins, defend cell biomembranes from lytic destruction in the presence of paraquat and 6-hydroxydopamine, and normalize the cell cycle. The protective effects of these compounds are associated with the suppression of oxidative stress, decreased expression of reactive oxygen species and nitric oxide formation in cells and normalization of mitochondrial function, and restoration of the mitochondrial membrane potential altered by neurotoxins. It was suggested that the neuroprotective activity of the studied 1,4-NQs is attributable to their pronounced antioxidant and free radical scavenging activity and their ability to reduce the amount of reactive oxygen species formed by paraquat and 6-hydroxydopamine action on neuronal cells. The significant correlation between the neuroprotective properties of 1,4-naphthoquinones and Quantitative Structure–Activity Relationship descriptors describing the physicochemical properties of these compounds means that the hydrophobicity, polarity, charge, and shape of the molecules can be of decisive importance in determining the biological activity of studied substances. View Full-Text
Keywords: 1,4-naphthoquinones; neuronal cells; paraquat; 6-hydroxydopamine; cell viability; reactive oxygen species and nitric oxide production; mitochondrial membrane potential; cell cycle; Parkinson’s disease; neurotoxicity; neuroprotection 1,4-naphthoquinones; neuronal cells; paraquat; 6-hydroxydopamine; cell viability; reactive oxygen species and nitric oxide production; mitochondrial membrane potential; cell cycle; Parkinson’s disease; neurotoxicity; neuroprotection
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MDPI and ACS Style

Menchinskaya, E.; Chingizova, E.; Pislyagin, E.; Likhatskaya, G.; Sabutski, Y.; Pelageev, D.; Polonik, S.; Aminin, D. Neuroprotective Effect of 1,4-Naphthoquinones in an In Vitro Model of Paraquat and 6-OHDA-Induced Neurotoxicity. Int. J. Mol. Sci. 2021, 22, 9933. https://doi.org/10.3390/ijms22189933

AMA Style

Menchinskaya E, Chingizova E, Pislyagin E, Likhatskaya G, Sabutski Y, Pelageev D, Polonik S, Aminin D. Neuroprotective Effect of 1,4-Naphthoquinones in an In Vitro Model of Paraquat and 6-OHDA-Induced Neurotoxicity. International Journal of Molecular Sciences. 2021; 22(18):9933. https://doi.org/10.3390/ijms22189933

Chicago/Turabian Style

Menchinskaya, Ekaterina, Ekaterina Chingizova, Evgeny Pislyagin, Galina Likhatskaya, Yuri Sabutski, Dmitry Pelageev, Sergei Polonik, and Dmitry Aminin. 2021. "Neuroprotective Effect of 1,4-Naphthoquinones in an In Vitro Model of Paraquat and 6-OHDA-Induced Neurotoxicity" International Journal of Molecular Sciences 22, no. 18: 9933. https://doi.org/10.3390/ijms22189933

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