title: Efficient Palladium-Triggered Release of Vorinostat from a Bioorthogonal Precursor.
abstract: Bioorthogonal uncaging strategies have recently emerged as an experimental therapeutic approach to control drug release. Herein we report a novel masking strategy that enables to modulate the metal chelating properties of hydroxamic acid groups by bioorthogonal chemistry using Pd-functionalized resins. This novel approach allowed to devise an inactive precursor of the histone deacetylase inhibitor vorinostat that was efficiently uncaged by heterogeneous Pd catalysis in cell culture models of glioma and lung cancer.
authors: Cancer Research UK Edinburgh Centre, Institute of Genetics and Molecular Medicine, University of Edinburgh , Crewe Road South, Edinburgh EH4 2XR, U.K.
authors: Belén
authors: B
authors: Rubio-Ruiz
authors: Cancer Research UK Edinburgh Centre, Institute of Genetics and Molecular Medicine, University of Edinburgh , Crewe Road South, Edinburgh EH4 2XR, U.K.
authors: Jason T
authors: JT
authors: Weiss
authors: Cancer Research UK Edinburgh Centre, Institute of Genetics and Molecular Medicine, University of Edinburgh , Crewe Road South, Edinburgh EH4 2XR, U.K.
authors: Asier
authors: A
authors: Unciti-Broceta
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002384:Catalysis; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D065546:Drug Liberation / Q000187:drug effects*; D004354:Drug Screening Assays, Antitumor; D056572:Histone Deacetylase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D006655:Histone Deacetylases / Q000378:metabolism; D006801:Humans; D006877:Hydroxamic Acids / Q000737:chemistry* / Q000494:pharmacology; D015394:Molecular Structure; D009942:Organometallic Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D010165:Palladium / Q000737:chemistry / Q000494:pharmacology*; D011355:Prodrugs / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured; D000077337:Vorinostat
chemical_list: D000970:Antineoplastic Agents; D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; D009942:Organometallic Compounds; D011355:Prodrugs; D000077337:Vorinostat; D010165:Palladium; D006655:Histone Deacetylases