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

Autor: Gonzalez G; Laboratory of Growth Regulators, Faculty of Science, Palacký University and the Institute of Experimental Botany of the Czech Academy of Sciences, Šlechtitelů 27, CZ-78371, Olomouc, Czech Republic; Department of Neurology, University Hospital Olomouc and Faculty of Medicine and Dentistry, Palacký University Olomouc, CZ-775 20, Olomouc, Czech Republic., Hodoň J; Department of Organic Chemistry, Faculty of Science, Palacky University, 17. Listopadu 1192/12, 771 46, Olomouc, Czech Republic., Kazakova A; Department of Organic Chemistry, Faculty of Science, Palacky University, 17. Listopadu 1192/12, 771 46, Olomouc, Czech Republic., D'Acunto CW; Laboratory of Growth Regulators, Faculty of Science, Palacký University and the Institute of Experimental Botany of the Czech Academy of Sciences, Šlechtitelů 27, CZ-78371, Olomouc, Czech Republic., Kaňovský P; Department of Neurology, University Hospital Olomouc and Faculty of Medicine and Dentistry, Palacký University Olomouc, CZ-775 20, Olomouc, Czech Republic., Urban M; Department of Medicinal Chemistry, Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacky University in Olomouc, Hnevotinska 5, 779 00, Olomouc, Czech Republic. Electronic address: milan.urban@upol.cz., Strnad M; Laboratory of Growth Regulators, Faculty of Science, Palacký University and the Institute of Experimental Botany of the Czech Academy of Sciences, Šlechtitelů 27, CZ-78371, Olomouc, Czech Republic; Department of Neurology, University Hospital Olomouc and Faculty of Medicine and Dentistry, Palacký University Olomouc, CZ-775 20, Olomouc, Czech Republic. Electronic address: miroslav.strnad@upol.cz.
Jazyk: angličtina
Zdroj: European journal of medicinal chemistry [Eur J Med Chem] 2021 Mar 05; Vol. 213, pp. 113168. Date of Electronic Publication: 2021 Jan 16.
DOI: 10.1016/j.ejmech.2021.113168
Abstrakt: 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.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2021 Elsevier Masson SAS. All rights reserved.)
Databáze: MEDLINE
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