Putative electron-affinic radiosensitizers and markers of hypoxic tissue: Synthesis and preliminary in vitro biological characterization of C3-amino-substituted benzotriazine dioxides (BTDOs).
Benzotriazine-1,4-dioxides (BTDOs)
Benzotriazine-1-monoxides (BTMOs)
Hypoxia-selective benzotriazines
Radiosensitization
Tirapazamine
Tumor hypoxia
Journal
European journal of medicinal chemistry
ISSN: 1768-3254
Titre abrégé: Eur J Med Chem
Pays: France
ID NLM: 0420510
Informations de publication
Date de publication:
01 Mar 2019
01 Mar 2019
Historique:
received:
26
11
2018
revised:
04
01
2019
accepted:
05
01
2019
pubmed:
27
1
2019
medline:
22
3
2019
entrez:
27
1
2019
Statut:
ppublish
Résumé
The redox characteristics of 1,2,4-benzotriazine-1,4-dioxides (BTDOs) make them potential radiosensitizing agents for hypoxic cells in solid human cancers. Tirapazamine (TPZ) is the most clinically tested BTDO radiosensitizer, despite its toxicity at effective doses. To date, no BTDOs have been developed as diagnostic markers of tissue hypoxia. TPZ analogues with appropriate reporting groups can act as potential radiosensitizers and hypoxia selective diagnostics. 3-Chloro-1,2,4-benzotriazine 1-oxide was substituted at the C3 position to afford 3-(2-hydroxyethoxyethyl)-amino-1,2,4-benzotriazine-1-oxide, which was oxidized to 3-(2-hydroxyethoxyethyl)-amino-1,2,4-benzotriazine-1,4-dioxide (HO-EOE-TPZ) or converted to 3-(2-tosyloxyethoxyethyl)-amino-1,2,4-benzotriazine-1,4-dioxide (Tos-EOE-TPZ). Tos-EOE-TPZ was intended for use as a synthon for preparing 3-(2-azidoethoxyethyl)-amino-1,2,4-benzotriazine-1,4-dioxide (N The LUMO, IC
Identifiants
pubmed: 30684798
pii: S0223-5234(19)30015-7
doi: 10.1016/j.ejmech.2019.01.009
pii:
doi:
Substances chimiques
Biomarkers
0
Oxides
0
Radiation-Sensitizing Agents
0
Triazines
0
Tirapazamine
1UD32YR59G
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
216-224Informations de copyright
Copyright © 2019 Elsevier Masson SAS. All rights reserved.