Interaction of Functionalized Naphthalenophanes with Abasic Sites in DNA: DNA Cleavage, DNA Cleavage Inhibition, and Formation of Ligand-DNA Adducts.
DNA cleavage
abasic sites
fluorescence
macrocyclic ligands
structure-activity relationships
Journal
Chemistry (Weinheim an der Bergstrasse, Germany)
ISSN: 1521-3765
Titre abrégé: Chemistry
Pays: Germany
ID NLM: 9513783
Informations de publication
Date de publication:
06 Feb 2019
06 Feb 2019
Historique:
received:
06
11
2018
revised:
30
11
2018
pubmed:
7
12
2018
medline:
1
8
2019
entrez:
4
12
2018
Statut:
ppublish
Résumé
Ligands interacting with abasic (AP) sites in DNA may generate roadblocks in base-excision DNA repair (BER) due to indirect inhibition of DNA repair enzymes (e.g., APE1) and/or formation of toxic byproducts, resulting from ligand-induced strand cleavage or covalent cross-links. Herein, a series of 12 putative AP-site ligands, sharing the common naphthalenophane scaffold, but endowed with a variety of substituents, have been prepared and systematically studied. The results demonstrate that most naphthalenophanes bind to AP sites in DNA and inhibit the APE1-induced hydrolysis of the latter in vitro. Remarkably, their APE1 inhibitory activity, as characterized by IC
Identifiants
pubmed: 30508326
doi: 10.1002/chem.201805555
doi:
Substances chimiques
DNA Adducts
0
Ligands
0
Naphthalenes
0
naphthalene
2166IN72UN
DNA
9007-49-2
Types de publication
Journal Article
Langues
eng
Pagination
1949-1962Subventions
Organisme : Agence Nationale de la Recherche
ID : ANR-11-IDEX-0003-02
Informations de copyright
© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.