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A Newly Identified Monoterpenoid-Based Small Molecule Able to Support the Survival of Primary Cultured Dopamine Neurons and Alleviate MPTP-Induced Toxicity In Vivo. / Kotliarova, Anastasiia; Podturkina, Alexandra V.; Pavlova, Alla V. et al.

In: Molecules, Vol. 27, No. 23, 8286, 12.2022.

Research output: Contribution to journal › Article › peer-review

Harvard

Kotliarova, A, Podturkina, AV, Pavlova, AV, Gorina, DS, Lastovka, AV, Ardashov, OV, Rogachev, AD, Izyurov, AE, Arefieva, AB, Kulikov, AV, Tolstikova, TG, Volcho, KP, Salakhutdinov, NF & Sidorova, Y 2022, 'A Newly Identified Monoterpenoid-Based Small Molecule Able to Support the Survival of Primary Cultured Dopamine Neurons and Alleviate MPTP-Induced Toxicity In Vivo', Molecules, vol. 27, no. 23, 8286. https://doi.org/10.3390/molecules27238286

APA

Kotliarova, A., Podturkina, A. V., Pavlova, A. V., Gorina, D. S., Lastovka, A. V., Ardashov, O. V., Rogachev, A. D., Izyurov, A. E., Arefieva, A. B., Kulikov, A. V., Tolstikova, T. G., Volcho, K. P., Salakhutdinov, N. F., & Sidorova, Y. (2022). A Newly Identified Monoterpenoid-Based Small Molecule Able to Support the Survival of Primary Cultured Dopamine Neurons and Alleviate MPTP-Induced Toxicity In Vivo. Molecules, 27(23), [8286]. https://doi.org/10.3390/molecules27238286

Vancouver

Kotliarova A, Podturkina AV, Pavlova AV, Gorina DS, Lastovka AV, Ardashov OV et al. A Newly Identified Monoterpenoid-Based Small Molecule Able to Support the Survival of Primary Cultured Dopamine Neurons and Alleviate MPTP-Induced Toxicity In Vivo. Molecules. 2022 Dec;27(23):8286. doi: 10.3390/molecules27238286

Author

Kotliarova, Anastasiia ; Podturkina, Alexandra V. ; Pavlova, Alla V. et al. / A Newly Identified Monoterpenoid-Based Small Molecule Able to Support the Survival of Primary Cultured Dopamine Neurons and Alleviate MPTP-Induced Toxicity In Vivo. In: Molecules. 2022 ; Vol. 27, No. 23.

BibTeX

@article{32e38109d0e644149723b82fef75b2b4,
title = "A Newly Identified Monoterpenoid-Based Small Molecule Able to Support the Survival of Primary Cultured Dopamine Neurons and Alleviate MPTP-Induced Toxicity In Vivo",
abstract = "Parkinson{\textquoteright}s disease (PD) is the most common age-related movement disorder characterized by the progressive loss of nigrostriatal dopaminergic neurons. To date, PD treatment strategies are mostly based on dopamine replacement medicines, which can alleviate motor symptoms but do not slow down the progression of neurodegeneration. Thus, there is a need for disease-modifying PD therapies. The aim of this work was to evaluate the neuroprotective effects of the novel compound PA96 on dopamine neurons in vivo and in vitro, assess its ability to alleviate motor deficits in MPTP- and haloperidol-based PD models, as well as PK profile and BBB penetration. PA96 was synthesized from (1R,2R,6S)-3-methyl-6-(prop-1-en-2-yl) cyclohex-3-ene-1,2-diol (Prottremin) using the original three-step stereoselective procedure. We found that PA96: (1) supported the survival of cultured n{\"a}ive dopamine neurons; (2) supported the survival of MPP+-challenged dopamine neurons in vitro and in vivo; (3) had chemically appropriate properties (synthesis, solubility, etc.); (4) alleviated motor deficits in MPTP- and haloperidol-based models of PD; (5) penetrated the blood–brain barrier in vivo; and (6) was eliminated from the bloodstream relative rapidly. In conclusion, the present article demonstrates the identification of PA96 as a lead compound for the future development of this compound into a clinically used drug.",
keywords = "dopamine neurons, drug development, epoxydiol, medicinal chemistry, MPTP, neurodegeneration, Parkinson{\textquoteright}s disease, Prottremin, small molecules, tyrosine hydroxylase, Parkinson Disease/drug therapy, Substantia Nigra, Humans, Mice, Inbred C57BL, Neuroprotective Agents/pharmacology, Animals, Monoterpenes/pharmacology, MPTP Poisoning/drug therapy, Dopaminergic Neurons, Mice, Haloperidol/pharmacology, Disease Models, Animal",
author = "Anastasiia Kotliarova and Podturkina, {Alexandra V.} and Pavlova, {Alla V.} and Gorina, {Daria S.} and Lastovka, {Anastasiya V.} and Ardashov, {Oleg V.} and Rogachev, {Artem D.} and Izyurov, {Arseniy E.} and Arefieva, {Alla B.} and Kulikov, {Alexander V.} and Tolstikova, {Tatyana G.} and Volcho, {Konstantin P.} and Salakhutdinov, {Nariman F.} and Yulia Sidorova",
note = "Publisher Copyright: {\textcopyright} 2022 by the authors.",
year = "2022",
month = dec,
doi = "10.3390/molecules27238286",
language = "English",
volume = "27",
journal = "Molecules",
issn = "1420-3049",
publisher = "Multidisciplinary Digital Publishing Institute (MDPI)",
number = "23",

}

RIS

TY - JOUR

T1 - A Newly Identified Monoterpenoid-Based Small Molecule Able to Support the Survival of Primary Cultured Dopamine Neurons and Alleviate MPTP-Induced Toxicity In Vivo

AU - Kotliarova, Anastasiia

AU - Podturkina, Alexandra V.

AU - Pavlova, Alla V.

AU - Gorina, Daria S.

AU - Lastovka, Anastasiya V.

AU - Ardashov, Oleg V.

AU - Rogachev, Artem D.

AU - Izyurov, Arseniy E.

AU - Arefieva, Alla B.

AU - Kulikov, Alexander V.

AU - Tolstikova, Tatyana G.

AU - Volcho, Konstantin P.

AU - Salakhutdinov, Nariman F.

AU - Sidorova, Yulia

N1 - Publisher Copyright: © 2022 by the authors.

PY - 2022/12

Y1 - 2022/12

N2 - Parkinson’s disease (PD) is the most common age-related movement disorder characterized by the progressive loss of nigrostriatal dopaminergic neurons. To date, PD treatment strategies are mostly based on dopamine replacement medicines, which can alleviate motor symptoms but do not slow down the progression of neurodegeneration. Thus, there is a need for disease-modifying PD therapies. The aim of this work was to evaluate the neuroprotective effects of the novel compound PA96 on dopamine neurons in vivo and in vitro, assess its ability to alleviate motor deficits in MPTP- and haloperidol-based PD models, as well as PK profile and BBB penetration. PA96 was synthesized from (1R,2R,6S)-3-methyl-6-(prop-1-en-2-yl) cyclohex-3-ene-1,2-diol (Prottremin) using the original three-step stereoselective procedure. We found that PA96: (1) supported the survival of cultured näive dopamine neurons; (2) supported the survival of MPP+-challenged dopamine neurons in vitro and in vivo; (3) had chemically appropriate properties (synthesis, solubility, etc.); (4) alleviated motor deficits in MPTP- and haloperidol-based models of PD; (5) penetrated the blood–brain barrier in vivo; and (6) was eliminated from the bloodstream relative rapidly. In conclusion, the present article demonstrates the identification of PA96 as a lead compound for the future development of this compound into a clinically used drug.

AB - Parkinson’s disease (PD) is the most common age-related movement disorder characterized by the progressive loss of nigrostriatal dopaminergic neurons. To date, PD treatment strategies are mostly based on dopamine replacement medicines, which can alleviate motor symptoms but do not slow down the progression of neurodegeneration. Thus, there is a need for disease-modifying PD therapies. The aim of this work was to evaluate the neuroprotective effects of the novel compound PA96 on dopamine neurons in vivo and in vitro, assess its ability to alleviate motor deficits in MPTP- and haloperidol-based PD models, as well as PK profile and BBB penetration. PA96 was synthesized from (1R,2R,6S)-3-methyl-6-(prop-1-en-2-yl) cyclohex-3-ene-1,2-diol (Prottremin) using the original three-step stereoselective procedure. We found that PA96: (1) supported the survival of cultured näive dopamine neurons; (2) supported the survival of MPP+-challenged dopamine neurons in vitro and in vivo; (3) had chemically appropriate properties (synthesis, solubility, etc.); (4) alleviated motor deficits in MPTP- and haloperidol-based models of PD; (5) penetrated the blood–brain barrier in vivo; and (6) was eliminated from the bloodstream relative rapidly. In conclusion, the present article demonstrates the identification of PA96 as a lead compound for the future development of this compound into a clinically used drug.

KW - dopamine neurons

KW - drug development

KW - epoxydiol

KW - medicinal chemistry

KW - MPTP

KW - neurodegeneration

KW - Parkinson’s disease

KW - Prottremin

KW - small molecules

KW - tyrosine hydroxylase

KW - Parkinson Disease/drug therapy

KW - Substantia Nigra

KW - Humans

KW - Mice, Inbred C57BL

KW - Neuroprotective Agents/pharmacology

KW - Animals

KW - Monoterpenes/pharmacology

KW - MPTP Poisoning/drug therapy

KW - Dopaminergic Neurons

KW - Mice

KW - Haloperidol/pharmacology

KW - Disease Models, Animal

UR - http://www.scopus.com/inward/record.url?scp=85143623898&partnerID=8YFLogxK

UR - https://www.mendeley.com/catalogue/5f521b1a-e05d-356f-8122-e871af19f4d5/

U2 - 10.3390/molecules27238286

DO - 10.3390/molecules27238286

M3 - Article

C2 - 36500381

AN - SCOPUS:85143623898

VL - 27

JO - Molecules

JF - Molecules

SN - 1420-3049

IS - 23

M1 - 8286

ER -

ID: 40811988