0546173 - ÚEB 2022 RIV FR eng J - Journal Article
Gonzalez, Gabriel - Hodoň, J. - Kazakova, A. - D'Acunto, Cosimo Walter - Kaňovský, P. - Urban, M. - Strnad, Miroslav
Novel pentacyclic triterpenes exhibiting strong neuroprotective activity in SH-SY5Y cells in salsolinol- and glutamate-induced neurodegeneration models.
European Journal of Medicinal Chemistry. Roč. 213, MAR 5 (2021), č. článku 113168. ISSN 0223-5234. E-ISSN 1768-3254
R&D Projects: GA ČR GA20-15621S
Institutional support: RVO:61389030
Keywords : Betulin * Betulinic acid * Caspase-3,7 * Glutamate * Mitochondria * Neuroprotection * Pentacyclic triterpenes * Salsolinol * SH-SY5Y cells * Triazole
OECD category: Biochemistry and molecular biology
Impact factor: 7.088, year: 2021
Method of publishing: Open access
Result website:
http://doi.org/10.1016/j.ejmech.2021.113168
DOI: https://doi.org/10.1016/j.ejmech.2021.113168

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-β-D-glucose substituent showed a highly potent neuroprotective effect. Further studies revealed that removal of tetraacetyl-β-D-glucose part (free triazole derivative 10) resulted in strong neuroprotection in the SAL model at 1 μM, 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.

Permanent Link: http://hdl.handle.net/11104/0322712