Cytoprotective activities of kinetin purine isosteres

Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61389030%3A_____%2F21%3A00545890" target="_blank" >RIV/61389030:_____/21:00545890 - isvavai.cz</a>
Alternative codes found
RIV/00098892:_____/21:N0000155 RIV/61989592:15310/21:73605065 RIV/00216224:14310/21:00121382
Result on the web
<a href="http://doi.org/10.1016/j.bmc.2021.115993" target="_blank" >http://doi.org/10.1016/j.bmc.2021.115993</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1016/j.bmc.2021.115993" target="_blank" >10.1016/j.bmc.2021.115993</a>

Result language
angličtina
Original language name
Cytoprotective activities of kinetin purine isosteres
Original language description
Kinetin (N6-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 Friedreich́s 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.
Czech name
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Czech description
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Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
30104 - Pharmacology and pharmacy

Project
Result was created during the realization of more than one project. More information in the Projects tab.
Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year
2021
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

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