title: Design, synthesis, and biological evaluation of 2-aminobenzanilide derivatives as potent and selective HDAC inhibitors.
abstract: Epigenetic regulation is an essential process for the normal functioning of genes. Therefore, targeting epigenetic dysregulation in cancer may be a valid therapeutic approach for the treatment of this severe disease. Histone deacetylases (HDACs) are enzymes involved in the regulation of epigenetic post-translational modifications; because they are overexpressed in many types of cancer, HDACs are valuable targets for the development of new anticancer agents. A large series of 2-aminobenzanilides linked at the 4'-position to α-amino acid amides, arenes, and heteroarenes through a methylene bridge were designed, synthesized, and tested as novel HDAC inhibitors. Several compounds showed IC(50)  values in the two-digit nanomolar range in hrHDAC1 inhibition assays, lower than that of the reference compound MS-275. They also showed interesting selectivity profiles, as confirmed by western blot assays.
authors.affiliation: Institute of Pharmaceutical Sciences, Albert-Ludwigs-Universität Freiburg, Albertstr. 25, 79104 Freiburg, Germany.
authors.forename: Diana A
authors.initials: DA
authors.lastname: Stolfa
authors.forename: Angela
authors.initials: A
authors.lastname: Stefanachi
authors.forename: Julia M
authors.initials: JM
authors.lastname: Gajer
authors.forename: Angela
authors.initials: A
authors.lastname: Nebbioso
authors.forename: Lucia
authors.initials: L
authors.lastname: Altucci
authors.forename: Saverio
authors.initials: S
authors.lastname: Cellamare
authors.forename: Manfred
authors.initials: M
authors.lastname: Jung
authors.forename: Angelo
authors.initials: A
authors.lastname: Carotti
mesh_terms: D000813:Anilides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D001549:Benzamides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D056572:Histone Deacetylase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D006655:Histone Deacetylases / Q000378:metabolism*; D006801:Humans; D015394:Molecular Structure; D011994:Recombinant Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured; D020298:U937 Cells
chemical_list: D000813:Anilides; D001549:Benzamides; D056572:Histone Deacetylase Inhibitors; D011994:Recombinant Proteins; D006655:Histone Deacetylases