Non-psychotropic cannabinoids as inhibitors of TET1 protein

J 2022

Non-psychotropic cannabinoids as inhibitors of TET1 protein

ANTONYOVÁ, Veronika, Zdeněk KEJÍK, Tereza BROGYANYI, Robert KAPLÁNEK, Kateřina VESELÁ et. al.

Basic information

Original name

Non-psychotropic cannabinoids as inhibitors of TET1 protein

Authors

ANTONYOVÁ, Veronika (203 Czech Republic), Zdeněk KEJÍK (203 Czech Republic), Tereza BROGYANYI (203 Czech Republic), Robert KAPLÁNEK (203 Czech Republic), Kateřina VESELÁ (203 Czech Republic), Nikita ABRAMENKO (203 Czech Republic), Tomáš OCELKA (203 Czech Republic), Michal MASAŘÍK (203 Czech Republic, belonging to the institution), Adam MATKOWSKI (616 Poland), Jakub GBUREK (616 Poland), Renata ABEL (616 Poland), Andrean GOEDE (276 Germany), Robert PREISSNER (276 Germany), Petr NOVOTNÝ (203 Czech Republic) and Milan JAKUBEK (203 Czech Republic, guarantor)

Edition

Bioorganic Chemistry, San Dieo, ACADEMIC PRESS INC ELSEVIER SCIENCE, 2022, 0045-2068

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

30105 Physiology

Country of publisher

Slovenia

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

URL

Impact factor

Impact factor: 5.100

RIV identification code

RIV/00216224:14110/22:00125768

Organization unit

Faculty of Medicine

DOI

http://dx.doi.org/10.1016/j.bioorg.2022.105793

UT WoS

000819757600001

Keywords in English

Cannabinoids; TET1 protein; Iron chelation; DNA methylation; Epigenetic

Abstract

V originále

Non-psychotropic cannabinoids (e.g., cannabidiol, cannabinol and cannabigerol) are contained in numerous alimentary and medicinal products. Therefore, predicting and studying their possible side effects, such as changes in DNA methylation, is an important task for assessing the safety of these products. Interference with TET enzymes by chelating ferrous ions can contribute to the altered methylation pattern. All tested cannabinoids displayed a strong affinity for Fe(II) ions. Cannabidiol and cannabinol exhibited potent inhibitory activities (IC50 = 4.8 and 6.27 μM, respectively) towards the TET1 protein, whereas cannabigerol had no effect on the enzyme activity. An in silico molecular docking study revealed marked binding potential within the catalytic cavity for CBD/CBN, but some affinity was also found for CBG, thus the total lack of activity remains unexplained. These results imply that cannabinoids could affect the activity of the TET1 protein not only due to their affinity for Fe(II) but also due to other types of interactions (e.g., hydrophobic interactions and hydrogen bonding).

Links

LM2018133, research and development project

Name: Český národní uzel Evropské infrastruktury pro translační medicínu (Acronym: EATRIS-ERIC-CZ)

Investor: Ministry of Education, Youth and Sports of the CR

NU21-08-00407, research and development project

Name: Funkční nanoroboti pro navigovanou kombinovanou nádorovou terapii

Investor: Ministry of Health of the CR, Subprogram 1 - standard

TN01000013, research and development project

Name: Personalizovaná medicína - diagnostika a terapie

Investor: Technology Agency of the Czech Republic, Personalized Medicine – Diagnostics and Therapy

Citovat

ANTONYOVÁ, Veronika, Zdeněk KEJÍK, Tereza BROGYANYI, Robert KAPLÁNEK, Kateřina VESELÁ, Nikita ABRAMENKO, Tomáš OCELKA, Michal MASAŘÍK, Adam MATKOWSKI, Jakub GBUREK, Renata ABEL, Andrean GOEDE, Robert PREISSNER, Petr NOVOTNÝ and Milan JAKUBEK. Non-psychotropic cannabinoids as inhibitors of TET1 protein. Bioorganic Chemistry. San Dieo: ACADEMIC PRESS INC ELSEVIER SCIENCE, 2022, vol. 124, July 2022, p. 1-8. ISSN 0045-2068. Available from: https://dx.doi.org/10.1016/j.bioorg.2022.105793.

@article{1851239,
   author = {Antonyová, Veronika and Kejík, Zdeněk and Brogyanyi, Tereza and Kaplánek, Robert and Veselá, Kateřina and Abramenko, Nikita and Ocelka, Tomáš and Masařík, Michal and Matkowski, Adam and Gburek, Jakub and Abel, Renata and Goede, Andrean and Preissner, Robert and Novotný, Petr and Jakubek, Milan},
   article_location = {San Dieo},
   article_number = {July 2022},
   doi = {http://dx.doi.org/10.1016/j.bioorg.2022.105793},
   keywords = {Cannabinoids; TET1 protein; Iron chelation; DNA methylation; Epigenetic},
   language = {eng},
   issn = {0045-2068},
   journal = {Bioorganic Chemistry},
   title = {Non-psychotropic cannabinoids as inhibitors of TET1 protein},
   url = {https://www.sciencedirect.com/science/article/pii/S0045206822001985},
   volume = {124},
   year = {2022}
}

TY  - JOUR
ID  - 1851239
AU  - Antonyová, Veronika - Kejík, Zdeněk - Brogyanyi, Tereza - Kaplánek, Robert - Veselá, Kateřina - Abramenko, Nikita - Ocelka, Tomáš - Masařík, Michal - Matkowski, Adam - Gburek, Jakub - Abel, Renata - Goede, Andrean - Preissner, Robert - Novotný, Petr - Jakubek, Milan
PY  - 2022
TI  - Non-psychotropic cannabinoids as inhibitors of TET1 protein
JF  - Bioorganic Chemistry
VL  - 124
IS  - July 2022
SP  - 1-8
EP  - 1-8
PB  - ACADEMIC PRESS INC ELSEVIER SCIENCE
SN  - 00452068
KW  - Cannabinoids
KW  - TET1 protein
KW  - Iron chelation
KW  - DNA methylation
KW  - Epigenetic
UR  - https://www.sciencedirect.com/science/article/pii/S0045206822001985
N2  - Non-psychotropic cannabinoids (e.g., cannabidiol, cannabinol and cannabigerol) are contained in numerous alimentary and medicinal products. Therefore, predicting and studying their possible side effects, such as changes in DNA methylation, is an important task for assessing the safety of these products. Interference with TET enzymes by chelating ferrous ions can contribute to the altered methylation pattern. All tested cannabinoids displayed a strong affinity for Fe(II) ions. Cannabidiol and cannabinol exhibited potent inhibitory activities (IC50 = 4.8 and 6.27 μM, respectively) towards the TET1 protein, whereas cannabigerol had no effect on the enzyme activity. An in silico molecular docking study revealed marked binding potential within the catalytic cavity for CBD/CBN, but some affinity was also found for CBG, thus the total lack of activity remains unexplained. These results imply that cannabinoids could affect the activity of the TET1 protein not only due to their affinity for Fe(II) but also due to other types of interactions (e.g., hydrophobic interactions and hydrogen bonding).
ER  -

ANTONYOVÁ, Veronika, Zdeněk KEJÍK, Tereza BROGYANYI, Robert KAPLÁNEK, Kateřina VESELÁ, Nikita ABRAMENKO, Tomáš OCELKA, Michal MASAŘÍK, Adam MATKOWSKI, Jakub GBUREK, Renata ABEL, Andrean GOEDE, Robert PREISSNER, Petr NOVOTNÝ and Milan JAKUBEK. Non-psychotropic cannabinoids as inhibitors of TET1 protein. \textit{Bioorganic Chemistry}. San Dieo: ACADEMIC PRESS INC ELSEVIER SCIENCE, 2022, vol.~124, July 2022, p.~1-8. ISSN~0045-2068. Available from: https://dx.doi.org/10.1016/j.bioorg.2022.105793.

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