Synthesis and evaluation of squaramide and thiosquaramide inhibitors of the DNA repair enzyme SNM1A.
Interstrand crosslink repair
Nuclease inhibitor
Nucleoside
SNM1A
Squaramide
Thiosquaramide
Zinc-binding group
Journal
Bioorganic & medicinal chemistry
ISSN: 1464-3391
Titre abrégé: Bioorg Med Chem
Pays: England
ID NLM: 9413298
Informations de publication
Date de publication:
15 09 2021
15 09 2021
Historique:
received:
03
06
2021
revised:
05
08
2021
accepted:
07
08
2021
pubmed:
6
9
2021
medline:
31
12
2021
entrez:
5
9
2021
Statut:
ppublish
Résumé
SNM1A is a zinc-dependent nuclease involved in the removal of interstrand crosslink lesions from DNA. Inhibition of interstrand crosslink repair enzymes such as SNM1A is a promising strategy for improving the efficacy of crosslinking chemotherapy drugs. Initial studies have demonstrated the feasibility of developing SNM1A inhibitors, but the full potential of this enzyme as a drug target has yet to be explored. Herein, the synthesis of a family of squaramide- and thiosquaramide-bearing nucleoside derivatives and their evaluation as SNM1A inhibitors is reported. A gel electrophoresis assay was used to identify nucleoside derivatives bearing an N-hydroxysquaramide or squaric acid moiety at the 3'-position, and a thymidine derivative bearing a 5'-thiosquaramide, as candidate SNM1A inhibitors. Quantitative IC
Identifiants
pubmed: 34482229
pii: S0968-0896(21)00377-1
doi: 10.1016/j.bmc.2021.116369
pmc: PMC8607331
pii:
doi:
Substances chimiques
Enzyme Inhibitors
0
squaramide
0
Quinine
A7V27PHC7A
DNA Repair Enzymes
EC 6.5.1.-
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
116369Informations de copyright
Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.
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