SEREN, Seda; JOLY, Jean-Patrick; VOISIN, Pierre; BOUCHAUD, Véronique; AUDRAN, Gérard; MARQUE, Sylvain R A; MELLET, Philippe

Métadonnées

Afficher la notice complète

Licence d’utilisation du document

SEREN, Seda
Centre de résonance magnétique des systèmes biologiques [CRMSB]

JOLY, Jean-Patrick

VOISIN, Pierre
Centre de résonance magnétique des systèmes biologiques [CRMSB]

Langue

Article de revue

Ce document a été publié dans

Journal of Medicinal Chemistry. 2022-07-14, vol. 65, n° 13, p. 9253-9266

Résumé en anglais

Current chemotherapies suffer low specificity and sometimes drug resistance. Neutrophil elastase activity in cancer is associated with poor prognosis and metastasis settlement. More generally, tumors harbor various and persistent protease activities unseen in healthy tissues. In an attempt to be more specific, we designed prodrugs that are activatable by neutrophil elastase. Upon activation, these alkoxyamine-based drugs release cytotoxic alkyl radicals that act randomly to prevent drug resistance. As a result, U87 glioblastoma cells displayed high level caspase 3/7 activation during the first hour of exposure in the presence of human neutrophil elastase and the prodrug in vitro. The apoptosis process and cell death occurred between 24 and 48 h after exposure with a half lethal concentration of 150 μM. These prodrugs are versatile and easy to synthetize and can be adapted to many enzymes.< Réduire

Mots clés en anglais

Antineoplastic Agents

Glioblastoma

Humans

Leukocyte Elastase

Neutrophils

Prodrugs

URI

https://oskar-bordeaux.fr/handle/20.500.12278/170440

Unités de recherche

Centre de Résonance Magnétique des Systèmes Biologiques (CRMSB) - UMR 5536