The Lipophilic Purine Nucleoside-Tdp1 Inhibitor-Enhances DNA Damage Induced by Topotecan In Vitro and Potentiates the Antitumor Effect of Topotecan In Vivo.
Animals
Mice
Humans
Topotecan
/ pharmacology
Phosphoric Diester Hydrolases
/ metabolism
Phosphodiesterase Inhibitors
/ pharmacology
Purine Nucleosides
Structure-Activity Relationship
Topoisomerase I Inhibitors
/ pharmacology
Esterases
/ metabolism
DNA Damage
DNA
DNA Topoisomerases, Type I
/ metabolism
DNA repair
Tdp1 inhibitor
inhibiting activity
lipophilic nucleosides
synergy
topoisomerase I
topotecan
tyrosyl-DNA phosphodiesterase 1
Journal
Molecules (Basel, Switzerland)
ISSN: 1420-3049
Titre abrégé: Molecules
Pays: Switzerland
ID NLM: 100964009
Informations de publication
Date de publication:
31 Dec 2022
31 Dec 2022
Historique:
received:
12
11
2022
revised:
20
12
2022
accepted:
28
12
2022
entrez:
8
1
2023
pubmed:
9
1
2023
medline:
11
1
2023
Statut:
epublish
Résumé
The use of cancer chemotherapy sensitizers is a promising approach to induce the effect of clinically used anticancer treatments. One of the interesting targets is Tyrosyl-DNA Phosphodiesterase 1 (Tdp1), a DNA-repair enzyme, that may prevent the action of clinical Topoisomerase 1 (Top1) inhibitors, such as topotecan (Tpc). Tdp1 eliminates covalent Top1-DNA (Top1c) complexes that appear under the action of topotecan and determines the cytotoxic effect of this drug. We hypothesize that Tdp1 inhibition would sensitize cells towards the effect of Tpc. Herein, we report the synthesis and study of lipophilic derivatives of purine nucleosides that efficiently suppress Tdp1 activity, with IC
Identifiants
pubmed: 36615517
pii: molecules28010323
doi: 10.3390/molecules28010323
pmc: PMC9822400
pii:
doi:
Substances chimiques
Topotecan
7M7YKX2N15
Phosphoric Diester Hydrolases
EC 3.1.4.-
Phosphodiesterase Inhibitors
0
Purine Nucleosides
0
Topoisomerase I Inhibitors
0
Esterases
EC 3.1.-
DNA
9007-49-2
DNA Topoisomerases, Type I
EC 5.99.1.2
TDP1 protein, human
EC 3.1.4.-
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Ministry of Science and Higher Education Russian Federation
ID : 075-15-2020-773
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