Novel pentacyclic triterpenes exhibiting strong neuroprotective activity in SH-SY5Y cells in salsolinol- and glutamate-induced neurodegeneration models

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61989592%3A15110%2F21%3A73610742" target="_blank" >RIV/61989592:15110/21:73610742 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/61389030:_____/21:00546173 RIV/61989592:15310/21:73610742 RIV/00098892:_____/21:N0000157

Výsledek na webu

<a href="https://www.sciencedirect.com/science/article/pii/S0223523421000179" target="_blank" >https://www.sciencedirect.com/science/article/pii/S0223523421000179</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.ejmech.2021.113168" target="_blank" >10.1016/j.ejmech.2021.113168</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Novel pentacyclic triterpenes exhibiting strong neuroprotective activity in SH-SY5Y cells in salsolinol- and glutamate-induced neurodegeneration models

Popis výsledku v původním jazyce

Novel triterpene derivatives were prepared and evaluated in salsolinol (SAL)- and glutamate (Glu)-induced models of neurodegeneration in neuron-like SH-SY5Y cells. Among the tested compounds, betulin triazole 4 bearing a tetraacetyl-beta-D-glucose substituent showed a highly potent neuroprotective effect. Further studies revealed that removal of tetraacetyl-beta-D-glucose part (free triazole derivative 10) resulted in strong neuroprotection in the SAL model at 1 mu M, but this derivative suffered from cytotoxicity at higher concentrations. Both compounds modulated oxidative stress and caspase-3,7 activity, but 10 showed a superior effect comparable to the Ac-DEVD-CHO inhibitor. Interestingly, while both 4 and 10 outperformed the positive controls in blocking mitochondrial permeability transition pore opening, only 4 demonstrated potent restoration of the mitochondrial membrane potential (MMP) in the model. Derivatives 4 and 10 also showed neuroprotection in the Glu model, with 10 exhibiting the strongest oxidative stress reducing effect among the tested compounds, while the neuroprotective activity of 4 was probably due recovery of the MMP. (C) 2021 Elsevier Masson SAS. All rights reserved.

Název v anglickém jazyce

Novel pentacyclic triterpenes exhibiting strong neuroprotective activity in SH-SY5Y cells in salsolinol- and glutamate-induced neurodegeneration models

Popis výsledku anglicky

Novel triterpene derivatives were prepared and evaluated in salsolinol (SAL)- and glutamate (Glu)-induced models of neurodegeneration in neuron-like SH-SY5Y cells. Among the tested compounds, betulin triazole 4 bearing a tetraacetyl-beta-D-glucose substituent showed a highly potent neuroprotective effect. Further studies revealed that removal of tetraacetyl-beta-D-glucose part (free triazole derivative 10) resulted in strong neuroprotection in the SAL model at 1 mu M, but this derivative suffered from cytotoxicity at higher concentrations. Both compounds modulated oxidative stress and caspase-3,7 activity, but 10 showed a superior effect comparable to the Ac-DEVD-CHO inhibitor. Interestingly, while both 4 and 10 outperformed the positive controls in blocking mitochondrial permeability transition pore opening, only 4 demonstrated potent restoration of the mitochondrial membrane potential (MMP) in the model. Derivatives 4 and 10 also showed neuroprotection in the Glu model, with 10 exhibiting the strongest oxidative stress reducing effect among the tested compounds, while the neuroprotective activity of 4 was probably due recovery of the MMP. (C) 2021 Elsevier Masson SAS. All rights reserved.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30107 - Medicinal chemistry

Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2021

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY

ISSN

0223-5234

e-ISSN

1768-3254

Svazek periodika

213

Číslo periodika v rámci svazku

MAR

Stát vydavatele periodika

FR - Francouzská republika

Počet stran výsledku

18

Strana od-do

"113168-1"-"113168-18"

Kód UT WoS článku

000629626600038

EID výsledku v databázi Scopus

2-s2.0-85099660198