Article

Projet
Nouvelles stratégies thérapeutiques pour le relarguage ciblé d'antitumoraux et autres agents thérapeutiques  
Martine DEMEUNYNCKIsabelle BAUSSANNE,   
Titre
Enzymatically Activated Glyco-Prodrugs of Doxorubicin Synthesized by a Catalysis-Free Diels−Alder Reaction  
[Full paper ]
Auteurs
D. Bliman, M. Demeunynck, P. Leblond, S. Meignan, I. Baussane, S. Fort
Edition
Bioconjugate Chem. 2018, 29, 2370−2381
Année
2018
Résumé
The severe side effects associated with the use of anthracycline anticancer agents continues to limit their use. Herein we describe the synthesis and preliminary biological evaluation of three enzymatically activatable doxorubicinoligosaccharide prodrugs. The synthetic protocol allows late stage variation of the carbohydrate and is compatible with the use of disaccharides such as lactose as well as more complex oligosaccharides such as xyloglucan oligomers. The enzymatic release of doxorubicin from the prodrugs by both protease (plasmin) and human carboxylesterases (hCE1 and 2) was demonstrated in vitro and the cytotoxic effect of the prodrugs was assayed on MCF-7 breast cancer cells.