Natural Products and Their Derivatives as Inhibitors of the DNA Repair Enzyme Tyrosyl-DNA Phosphodiesterase 1.
TDP1 inhibitors
TOP1 inhibitors
anticancer therapy
derivative
natural compound
Journal
International journal of molecular sciences
ISSN: 1422-0067
Titre abrégé: Int J Mol Sci
Pays: Switzerland
ID NLM: 101092791
Informations de publication
Date de publication:
17 Mar 2023
17 Mar 2023
Historique:
received:
09
02
2023
revised:
22
02
2023
accepted:
14
03
2023
medline:
30
3
2023
entrez:
29
3
2023
pubmed:
30
3
2023
Statut:
epublish
Résumé
Tyrosyl-DNA phosphodiesterase 1 (TDP1) is an important repair enzyme that removes various covalent adducts from the 3' end of DNA. Particularly, covalent complexes of topoisomerase 1 (TOP1) with DNA stabilized by DNA damage or by various chemical agents are an examples of such adducts. Anticancer drugs such as the TOP1 poisons topotecan and irinotecan are responsible for the stabilization of these complexes. TDP1 neutralizes the effect of these anticancer drugs, eliminating the DNA adducts. Therefore, the inhibition of TDP1 can sensitize tumor cells to the action of TOP1 poisons. This review contains information about methods for determining the TDP1 activity, as well as describing the inhibitors of these enzyme derivatives of natural biologically active substances, such as aminoglycosides, nucleosides, polyphenolic compounds, and terpenoids. Data on the efficiency of combined inhibition of TOP1 and TDP1 in vitro and in vivo are presented.
Identifiants
pubmed: 36982848
pii: ijms24065781
doi: 10.3390/ijms24065781
pmc: PMC10051138
pii:
doi:
Substances chimiques
tyrosyl-DNA phosphodiesterase
EC 3.1.4.-
Biological Products
0
Phosphoric Diester Hydrolases
EC 3.1.4.-
DNA Repair Enzymes
EC 6.5.1.-
Antineoplastic Agents
0
DNA Topoisomerases, Type I
EC 5.99.1.2
DNA
9007-49-2
Types de publication
Journal Article
Review
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Russian Science Foundation
ID : 21-14-00105
Organisme : state assignments to ICBFM SB RAS
ID : 121031300041-4
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