Design of pH responsive clickable prodrugs applied to histone deacetylase inhibitors: A new strategy for anticancer therapy

Régis Delatouche (1) , Iza Denis (2, 3) , Marion Grinda (1) , Fatima El Bahhaj (1) , Estelle Baucher (2, 3) , Floraine Collette (4, 5) , Valérie Héroguez (4, 5) , Marc Grégoire (2, 3) , Christophe Blanquart (3, 2) , Philippe Bertrand (1)

1 IC2MP [Poitiers] - Institut de chimie des milieux et matériaux de Poitiers [UMR 7285]
2 CRCNA - Centre de Recherche en Cancérologie Nantes-Angers
3 UN - Université de Nantes
4 LCPO - Laboratoire de Chimie des Polymères Organiques
5 Team 1 LCPO : Polymerization Catalyses & Engineering

The aim of this study was to develop clickable prodrugs bearing a tunable pH responsive linker designed for acidic pH-mediated release of histone deacetylase inhibitors. HDACi are an important class of molecules belonging to the epigenetic modulators used for innovative cancer strategies. The behavior of these prodrugs was determined by a bioluminescence resonance energy transfer assay in living tumor cells. This work demonstrated that this innovative type of clickable prodrugs entered cancer cells and showed restored anti proliferative properties attributed to the effective release of the HDAC inhibitors. A correlation between kinetic studies, dose responses, and biological activities was obtained, making such clickable prodrugs good candidates for new strategies in epigenetic-oriented anticancer therapies

Domaines: Chimie

Régis Delatouche, Iza Denis, Marion Grinda, Fatima El Bahhaj, Estelle Baucher, et al.. Design of pH responsive clickable prodrugs applied to histone deacetylase inhibitors: A new strategy for anticancer therapy. European Journal of Pharmaceutics and Biopharmaceutics, 2013, 85 (3), pp.862-872. ⟨10.1016/j.ejpb.2013.03.006⟩. ⟨hal-04074175⟩