Оценка Эффективности Превентивной Терапии С Индуктором Шаперонов U133 В Модели Доклинической Стадии Болезни Паркинсона У Пожилых Крыс

Белан, Дарья Владимировна; Полоник, С. Г.; Екимова, И. В.

doi:10.31857/s0869813920100027

Cited by 2 publications

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“…Recently, therapy based on U-133 administration was applied in a model of the preclinical stage of PD in elderly rats. It was shown that U-133 weakened the process of neurodegeneration in the substantia nigra pars compacta and counteracted the development of neuroinflammation, decreased the amount of aggregated α-synuclein and regression of post-translationally modified α-synuclein, eliminated anhedonia, and prevented the development of neurodegeneration in monoaminergic emetogenic structures of the brain in experimental PD [13,15]. Therefore, the study of the neuroprotective effects of 1,4-naphthoquinones in general and their antiparkinsonian activity in particular may have good prospects.…”

Section: Discussionmentioning

confidence: 99%

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

Menchinskaya

Chingizova

Pislyagin

et al. 2021

IJMS

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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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Section: Discussionmentioning

confidence: 99%

“…Their role in protecting against neurodegenerative diseases such as Alzheimer's disease (AD) and Parkinson's disease has also been established [4][5][6][7][8][9][10][11][12]. One of the 1,4-NQs synthesized by our group, U-133, exhibited a promising neuroprotective effect in an in vivo PD rat model [13].…”

Section: Introductionmentioning

confidence: 95%

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

Menchinskaya

Chingizova

Pislyagin

et al. 2021

IJMS

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Synthesis, Cytotoxic Activity Evaluation and Quantitative Structure-ActivityAnalysis of Substituted 5,8-Dihydroxy-1,4-naphthoquinones and Their O- and S-Glycoside Derivatives Tested against Neuro-2a Cancer Cells

et al. 2020

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Based on 6,7-substituted 2,5,8-trihydroxy-1,4-naphtoquinones (1,4-NQs) derived from sea urchins, five new acetyl-O-glucosides of NQs were prepared. A new method of conjugation of per-O-acetylated 1-mercaptosaccharides with 2-hydroxy-1,4-NQs through a methylene spacer was developed. Methylation of 2-hydroxy group of quinone core of acetylthiomethylglycosides by diazomethane and deacetylation of sugar moiety led to 28 new thiomethylglycosidesof 2-hydroxy- and 2-methoxy-1,4-NQs. The cytotoxic activity of starting 1,4-NQs (13 compounds) and their O- and S-glycoside derivatives (37 compounds) was determined by the MTT method against Neuro-2a mouse neuroblastoma cells. Cytotoxic compounds with EC50 = 2.7–87.0 μM and nontoxic compounds with EC50 > 100 μM were found. Acetylated O- and S-glycosides 1,4-NQs were the most potent, with EC50 = 2.7–16.4 μM. Methylation of the 2-OH group innaphthoquinone core led to a sharp increase in the cytotoxic activity of acetylated thioglycosidesof NQs, which was partially retained for their deacetylated derivatives. Thiomethylglycosides of 2-hydroxy-1,4-NQs with OH and MeO groups in quinone core at positions 6 and 7, resprectively formed a nontoxic set of compounds with EC50 > 100 μM. A quantitative structure-activity relationship (QSAR) model of cytotoxic activity of 22 1,4-NQ derivatives was constructed and tested. Descriptors related to the cytotoxic activity of new 1,4-NQ derivatives were determined. The QSAR model is good at predicting the activity of 1,4-NQ derivatives which are unused for QSAR models and nontoxic derivatives.

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Оценка Эффективности Превентивной Терапии С Индуктором Шаперонов U133 В Модели Доклинической Стадии Болезни Паркинсона У Пожилых Крыс

Cited by 2 publications

References 0 publications

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

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

Synthesis, Cytotoxic Activity Evaluation and Quantitative Structure-ActivityAnalysis of Substituted 5,8-Dihydroxy-1,4-naphthoquinones and Their O- and S-Glycoside Derivatives Tested against Neuro-2a Cancer Cells

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