Targeting of the Mitochondrial TET1 Protein by Pyrrolo[3,2-b]pyrrole Chelators

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216224%3A90127%2F22%3A00140002" target="_blank" >RIV/00216224:90127/22:00140002 - isvavai.cz</a>

Alternative codes found

RIV/00216208:11110/22:10448557 RIV/00064165:_____/22:10448557

Result on the web

<a href="https://www.mdpi.com/1422-0067/23/18/10850" target="_blank" >https://www.mdpi.com/1422-0067/23/18/10850</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.3390/ijms231810850" target="_blank" >10.3390/ijms231810850</a>

Result language

angličtina

Original language name

Targeting of the Mitochondrial TET1 Protein by Pyrrolo[3,2-b]pyrrole Chelators

Original language description

Targeting of epigenetic mechanisms, such as the hydroxymethylation of DNA, has been intensively studied, with respect to the treatment of many serious pathologies, including oncological disorders. Recent studies demonstrated that promising therapeutic strategies could potentially be based on the inhibition of the TET1 protein (ten-eleven translocation methylcytosine dioxygenase 1) by specific iron chelators. Therefore, in the present work, we prepared a series of pyrrolopyrrole derivatives with hydrazide (1) or hydrazone (2-6) iron-binding groups. As a result, we determined that the basic pyrrolo[3,2-b]pyrrole derivative 1 was a strong inhibitor of the TET1 protein (IC50 = 1.33 mu M), supported by microscale thermophoresis and molecular docking. Pyrrolo[3,2-b]pyrroles 2-6, bearing substituted 2-hydroxybenzylidene moieties, displayed no significant inhibitory activity. In addition, in vitro studies demonstrated that derivative 1 exhibits potent anticancer activity and an exclusive mitochondrial localization, confirmed by Pearson's correlation coefficient of 0.92.

Czech name

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Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

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OECD FORD branch

10608 - Biochemistry and molecular biology

Project

Result was created during the realization of more than one project. More information in the Projects tab.

Continuities

—

Publication year

2022

Confidentiality

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

Name of the periodical

International Journal of Molecular Sciences

ISSN

1422-0067

e-ISSN

1661-6596

Volume of the periodical

23

Issue of the periodical within the volume

18

Country of publishing house

CH - SWITZERLAND

Number of pages

25

Pages from-to

10850

UT code for WoS article

000858770200001

EID of the result in the Scopus database

2-s2.0-85138892878