Neuroprotective Effect of 2-(Benzyloxy)arylureas Is Not Related to CypD Inhibition nor Suppression of mPTP Opening

Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F62690094%3A18470%2F24%3A50021758" target="_blank" >RIV/62690094:18470/24:50021758 - isvavai.cz</a>
Alternative codes found
RIV/00216208:11150/24:10486740
Result on the web
<a href="https://pubs.acs.org/doi/abs/10.1021/acsmedchemlett.4c00353" target="_blank" >https://pubs.acs.org/doi/abs/10.1021/acsmedchemlett.4c00353</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1021/acsmedchemlett.4c00353" target="_blank" >10.1021/acsmedchemlett.4c00353</a>

Result language
angličtina
Original language name
Neuroprotective Effect of 2-(Benzyloxy)arylureas Is Not Related to CypD Inhibition nor Suppression of mPTP Opening
Original language description
Cyclophilin D (CypD) is a mitochondrial enzyme widely accepted as a regulator of the mitochondrial permeability transition pore (mPTP). Excessive opening of mPTP is associated with mitochondrial dysfunction and the development of various diseases; thus, suppression of mPTP opening through CypD inhibition presents a promising therapeutic approach. However, only a limited number of selective CypD inhibitors are currently available. In this study, 10 derivatives of 2-(benzyloxy)arylurea similar or identical to previously published CypD/mPTP inhibitors were synthesized. Unlike the original reports that assessed the opening of mPTP at the cellular level, the compounds were tested directly on the purified CypD enzyme to validate their putative mechanism of action. Additionally, the effect of the selected compounds was tested on isolated mitochondria. The obtained results show that the compounds are only weak inhibitors of CypD and mPTP opening, which is in contrast to previous conclusions drawn from the unspecific cellular JC-1 assay.
Czech name
—
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
—
OECD FORD branch
30107 - Medicinal chemistry

Project
<a href="/en/project/NU22J-02-00006" target="_blank" >NU22J-02-00006: Small-molecule inhibitors of mitochondrial permeability transition for treatment of myocardial ischemia-reperfusion injury</a><br>
Continuities
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Publication year
2024
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

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