Article (Scientific journals)
Inhibition studies of DNA methyltransferases by maleimide derivatives of RG108 as non-nucleoside inhibitors
Rondelet, Grégoire; Fleury, Laurence; Faux, Céline et al.
2017In Future Medicinal Chemistry, 9 (13)
Peer Reviewed verified by ORBi
 

Files


Full Text
Rondelet 2017.pdf
Publisher postprint (4.48 MB)
Request a copy

All documents in ORBi are protected by a user license.

Send to



Details



Keywords :
apoenzyme crystal structure; DNA methylation; DNA methyltransferases; epigenetics; Michael acceptor
Abstract :
[en] Aim: DNA methyltransferases (DNMTs) are important drug targets for epigenetic therapy of cancer. Nowadays, non-nucleoside DNMT inhibitors are in development to address high toxicity of nucleoside analogs. However, these compounds still have low activity in cancer cells and mode of action of these compounds remains unclear. Materials & methods: In this work, we studied maleimide derivatives of RG108 by biochemical, structural and computational approaches to highlight their inhibition mechanism on DNMTs. Results: Findings demonstrated a correlation between cytotoxicity on mesothelioma cells of these compounds and their inhibitory potency against DNMTs. Noncovalent and covalent docking studies, supported by crystallographic (apo structure of M.HhaI) and differential scanning fluorimetry assays, provided detailed insights into their mode of action and revealed essential residues for the stabilization of such compounds inside DNMTs.
Research center :
CNRS
Disciplines :
Oncology
Oncology
Author, co-author :
Rondelet, Grégoire;  U Namur > Department of Chemistry
Fleury, Laurence
Faux, Céline
Masson, Véronique
Dubois, Jean
Arimondo, Paola
Willems, Luc  ;  Université de Liège - ULiège > Agronomie, Bio-ingénierie et Chimie (AgroBioChem) > Microbial, food and biobased technologies
Wouters, Johan
Language :
English
Title :
Inhibition studies of DNA methyltransferases by maleimide derivatives of RG108 as non-nucleoside inhibitors
Publication date :
10 August 2017
Journal title :
Future Medicinal Chemistry
ISSN :
1756-8919
eISSN :
1756-8927
Publisher :
Future Science, United Kingdom
Volume :
9
Issue :
13
Peer reviewed :
Peer Reviewed verified by ORBi
Funders :
F.R.S.-FNRS - Fonds de la Recherche Scientifique [BE]
the Fondation InNaBioSanté
the National Research Agency
Investissement d’avenir
Available on ORBi :
since 31 January 2018

Statistics


Number of views
44 (5 by ULiège)
Number of downloads
1 (1 by ULiège)

Scopus citations®
 
23
Scopus citations®
without self-citations
21
OpenCitations
 
20

Bibliography


Similar publications



Contact ORBi