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

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 r...

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Autores principales: Menchinskaya, Ekaterina, Chingizova, Ekaterina, Pislyagin, Evgeny, Likhatskaya, Galina, Sabutski, Yuri, Pelageev, Dmitry, Polonik, Sergei, Aminin, Dmitry
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8468277/
https://www.ncbi.nlm.nih.gov/pubmed/34576094
http://dx.doi.org/10.3390/ijms22189933
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author Menchinskaya, Ekaterina
Chingizova, Ekaterina
Pislyagin, Evgeny
Likhatskaya, Galina
Sabutski, Yuri
Pelageev, Dmitry
Polonik, Sergei
Aminin, Dmitry
author_facet Menchinskaya, Ekaterina
Chingizova, Ekaterina
Pislyagin, Evgeny
Likhatskaya, Galina
Sabutski, Yuri
Pelageev, Dmitry
Polonik, Sergei
Aminin, Dmitry
author_sort Menchinskaya, Ekaterina
collection PubMed
description 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.
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spelling pubmed-84682772021-09-27 Neuroprotective Effect of 1,4-Naphthoquinones in an In Vitro Model of Paraquat and 6-OHDA-Induced Neurotoxicity Menchinskaya, Ekaterina Chingizova, Ekaterina Pislyagin, Evgeny Likhatskaya, Galina Sabutski, Yuri Pelageev, Dmitry Polonik, Sergei Aminin, Dmitry Int J Mol Sci Article 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. MDPI 2021-09-14 /pmc/articles/PMC8468277/ /pubmed/34576094 http://dx.doi.org/10.3390/ijms22189933 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Menchinskaya, Ekaterina
Chingizova, Ekaterina
Pislyagin, Evgeny
Likhatskaya, Galina
Sabutski, Yuri
Pelageev, Dmitry
Polonik, Sergei
Aminin, Dmitry
Neuroprotective Effect of 1,4-Naphthoquinones in an In Vitro Model of Paraquat and 6-OHDA-Induced Neurotoxicity
title Neuroprotective Effect of 1,4-Naphthoquinones in an In Vitro Model of Paraquat and 6-OHDA-Induced Neurotoxicity
title_full Neuroprotective Effect of 1,4-Naphthoquinones in an In Vitro Model of Paraquat and 6-OHDA-Induced Neurotoxicity
title_fullStr Neuroprotective Effect of 1,4-Naphthoquinones in an In Vitro Model of Paraquat and 6-OHDA-Induced Neurotoxicity
title_full_unstemmed Neuroprotective Effect of 1,4-Naphthoquinones in an In Vitro Model of Paraquat and 6-OHDA-Induced Neurotoxicity
title_short Neuroprotective Effect of 1,4-Naphthoquinones in an In Vitro Model of Paraquat and 6-OHDA-Induced Neurotoxicity
title_sort neuroprotective effect of 1,4-naphthoquinones in an in vitro model of paraquat and 6-ohda-induced neurotoxicity
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8468277/
https://www.ncbi.nlm.nih.gov/pubmed/34576094
http://dx.doi.org/10.3390/ijms22189933
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