Cytoprotective activities of kinetin purine isosteres

J 2021

Cytoprotective activities of kinetin purine isosteres

MAKOVÁ, Barbara, Václav MIK, Barbora LIŠKOVÁ, Gabriel GONZALEZ, Dominik VÍTEK et. al.

Základní údaje

Originální název

Cytoprotective activities of kinetin purine isosteres

Autoři

MAKOVÁ, Barbara, Václav MIK, Barbora LIŠKOVÁ, Gabriel GONZALEZ, Dominik VÍTEK, Martina MEDVEDÍKOVÁ, Beata MONFORT, Veronika RUČILOVÁ, Alena KADLECOVÁ, Prashant KHIRSARIYA (356 Indie, domácí), Zoila Gándara BARREIRO, Libor HAVLÍČEK, Marek ZATLOUKAL, Miroslav SOURAL, Kamil PARUCH (203 Česká republika, domácí), Benoit D'AUTRÉAUX, Marián HAJDÚCH, Miroslav STRNAD a Jiří VOLLER (garant)

Vydání

Bioorganic and Medicinal Chemistry, Oxford, Elsevier Ltd, 2021, 0968-0896

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

10608 Biochemistry and molecular biology

Stát vydavatele

Velká Británie a Severní Irsko

Utajení

není předmětem státního či obchodního tajemství

Odkazy

URL

Impakt faktor

Impact factor: 3.461

Kód RIV

RIV/00216224:14310/21:00121382

Organizační jednotka

Přírodovědecká fakulta

DOI

http://dx.doi.org/10.1016/j.bmc.2021.115993

UT WoS

000623635000002

Klíčová slova anglicky

Cytokinin; Kinetin; bioisostery - Friedreichs ataxia; Mitoprotection - familial dysautonomia; Neuroprotection

Štítky

rivok

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 9. 4. 2021 08:50, Mgr. Marie Šípková, DiS.

Anotace

V originále

Kinetin (N-6-furfuryladenine), a plant growth substance of the cytokinin family, has been shown to modulate aging and various age-related conditions in animal models. Here we report the synthesis of kinetin isosteres with the purine ring replaced by other bicyclic heterocycles, and the biological evaluation of their activity in several in vitro models related to neurodegenerative diseases. Our findings indicate that kinetin isosteres protect Friedreich's ataxia patient-derived fibroblasts against glutathione depletion, protect neuron-like SH-SY5Y cells from glutamate-induced oxidative damage, and correct aberrant splicing of the ELP1 gene in fibroblasts derived from a familial dysautonomia patient. Although the mechanism of action of kinetin derivatives remains unclear , our data suggest that the cytoprotective activity of some purine isosteres is mediated by their ability to reduce oxidative stress. Further, the studies of permeation across artificial membrane and model gut and blood-brain barriers indicate that the compounds are orally available and can reach central nervous system. Overall, our data demonstrate that isosteric replacement of the kinetin purine scaffold is a fruitful strategy for improving known biological activities of kinetin and discovering novel therapeutic opportunities.

Návaznosti

EF16_025/0007381, projekt VaV

Název: Preklinická progrese nových organických sloučenin s cílenou biologickou aktivitou

Citovat

MAKOVÁ, Barbara, Václav MIK, Barbora LIŠKOVÁ, Gabriel GONZALEZ, Dominik VÍTEK, Martina MEDVEDÍKOVÁ, Beata MONFORT, Veronika RUČILOVÁ, Alena KADLECOVÁ, Prashant KHIRSARIYA, Zoila Gándara BARREIRO, Libor HAVLÍČEK, Marek ZATLOUKAL, Miroslav SOURAL, Kamil PARUCH, Benoit D'AUTRÉAUX, Marián HAJDÚCH, Miroslav STRNAD a Jiří VOLLER. Cytoprotective activities of kinetin purine isosteres. Bioorganic and Medicinal Chemistry. Oxford: Elsevier Ltd, 2021, roč. 33, March, s. "115993", 14 s. ISSN 0968-0896. Dostupné z: https://dx.doi.org/10.1016/j.bmc.2021.115993.

@article{1758536,
   author = {Maková, Barbara and Mik, Václav and Lišková, Barbora and Gonzalez, Gabriel and Vítek, Dominik and Medvedíková, Martina and Monfort, Beata and Ručilová, Veronika and Kadlecová, Alena and Khirsariya, Prashant and Barreiro, Zoila Gándara and Havlíček, Libor and Zatloukal, Marek and Soural, Miroslav and Paruch, Kamil and D'Autréaux, Benoit and Hajdúch, Marián and Strnad, Miroslav and Voller, Jiří},
   article_location = {Oxford},
   article_number = {March},
   doi = {http://dx.doi.org/10.1016/j.bmc.2021.115993},
   keywords = {Cytokinin; Kinetin; bioisostery - Friedreichs ataxia; Mitoprotection - familial dysautonomia; Neuroprotection},
   language = {eng},
   issn = {0968-0896},
   journal = {Bioorganic and Medicinal Chemistry},
   title = {Cytoprotective activities of kinetin purine isosteres},
   url = {https://doi.org/10.1016/j.bmc.2021.115993},
   volume = {33},
   year = {2021}
}

TY  - JOUR
ID  - 1758536
AU  - Maková, Barbara - Mik, Václav - Lišková, Barbora - Gonzalez, Gabriel - Vítek, Dominik - Medvedíková, Martina - Monfort, Beata - Ručilová, Veronika - Kadlecová, Alena - Khirsariya, Prashant - Barreiro, Zoila Gándara - Havlíček, Libor - Zatloukal, Marek - Soural, Miroslav - Paruch, Kamil - D'Autréaux, Benoit - Hajdúch, Marián - Strnad, Miroslav - Voller, Jiří
PY  - 2021
TI  - Cytoprotective activities of kinetin purine isosteres
JF  - Bioorganic and Medicinal Chemistry
VL  - 33
IS  - March
SP  - "115993"
EP  - "115993"
PB  - Elsevier Ltd
SN  - 09680896
KW  - Cytokinin
KW  - Kinetin
KW  - bioisostery - Friedreichs ataxia
KW  - Mitoprotection - familial dysautonomia
KW  - Neuroprotection
UR  - https://doi.org/10.1016/j.bmc.2021.115993
N2  - Kinetin (N-6-furfuryladenine), a plant growth substance of the cytokinin family, has been shown to modulate aging and various age-related conditions in animal models. Here we report the synthesis of kinetin isosteres with the purine ring replaced by other bicyclic heterocycles, and the biological evaluation of their activity in several in vitro models related to neurodegenerative diseases. Our findings indicate that kinetin isosteres protect Friedreich's ataxia patient-derived fibroblasts against glutathione depletion, protect neuron-like SH-SY5Y cells from glutamate-induced oxidative damage, and correct aberrant splicing of the ELP1 gene in fibroblasts derived from a familial dysautonomia patient. Although the mechanism of action of kinetin derivatives remains unclear , our data suggest that the cytoprotective activity of some purine isosteres is mediated by their ability to reduce oxidative stress. Further, the studies of permeation across artificial membrane and model gut and blood-brain barriers indicate that the compounds are orally available and can reach central nervous system. Overall, our data demonstrate that isosteric replacement of the kinetin purine scaffold is a fruitful strategy for improving known biological activities of kinetin and discovering novel therapeutic opportunities.
ER  -

MAKOVÁ, Barbara, Václav MIK, Barbora LIŠKOVÁ, Gabriel GONZALEZ, Dominik VÍTEK, Martina MEDVEDÍKOVÁ, Beata MONFORT, Veronika RUČILOVÁ, Alena KADLECOVÁ, Prashant KHIRSARIYA, Zoila Gándara BARREIRO, Libor HAVLÍČEK, Marek ZATLOUKAL, Miroslav SOURAL, Kamil PARUCH, Benoit D'AUTRÉAUX, Marián HAJDÚCH, Miroslav STRNAD a Jiří VOLLER. Cytoprotective activities of kinetin purine isosteres. \textit{Bioorganic and Medicinal Chemistry}. Oxford: Elsevier Ltd, 2021, roč.~33, March, s.~''115993'', 14 s. ISSN~0968-0896. Dostupné z: https://dx.doi.org/10.1016/j.bmc.2021.115993.

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