title: Design of pH responsive clickable prodrugs applied to histone deacetylase inhibitors: a new strategy for anticancer therapy.
abstract: 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.
authors.affiliation: Institut de Chimie des Milieux et Matériaux de Poitiers, CNRS, UMR 7285, Université de Poitiers, Poitiers cedex, France.
authors.forename: Régis
authors.initials: R
authors.lastname: Delatouche
authors.forename: Iza
authors.initials: I
authors.lastname: Denis
authors.forename: Marion
authors.initials: M
authors.lastname: Grinda
authors.forename: Fatima
authors.initials: F
authors.lastname: El Bahhaj
authors.forename: Estelle
authors.initials: E
authors.lastname: Baucher
authors.forename: Floraine
authors.initials: F
authors.lastname: Collette
authors.forename: Valérie
authors.initials: V
authors.lastname: Héroguez
authors.forename: Marc
authors.initials: M
authors.lastname: Grégoire
authors.forename: Christophe
authors.initials: C
authors.lastname: Blanquart
authors.forename: Philippe
authors.initials: P
authors.lastname: Bertrand
mesh_terms: D000107:Acetylation; D000230:Adenocarcinoma / Q000188:drug therapy; D000970:Antineoplastic Agents / Q000737:chemistry*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival; D002626:Chemistry, Pharmaceutical / Q000379:methods; D057930:Click Chemistry / Q000379:methods*; D015195:Drug Design; D004735:Energy Transfer; D044127:Epigenesis, Genetic; D056572:Histone Deacetylase Inhibitors / Q000737:chemistry*; D006657:Histones / Q000737:chemistry; D006801:Humans; D006863:Hydrogen-Ion Concentration; D020128:Inhibitory Concentration 50; D007700:Kinetics; D049449:Luminescence; D008175:Lung Neoplasms / Q000188:drug therapy*; D008654:Mesothelioma / Q000188:drug therapy; D009369:Neoplasms / Q000188:drug therapy*; D011355:Prodrugs / Q000737:chemistry*
chemical_list: D000970:Antineoplastic Agents; D056572:Histone Deacetylase Inhibitors; D006657:Histones; D011355:Prodrugs
keywords: Bioluminescence; Cancer; Click chemistry; Histone acetylation; Prodrug; pH response