1. Design, synthesis, and biological evaluation of 2-aminobenzanilide derivatives as potent and selective HDAC inhibitors.
- Author
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Stolfa DA, Stefanachi A, Gajer JM, Nebbioso A, Altucci L, Cellamare S, Jung M, and Carotti A
- Subjects
- Anilides chemical synthesis, Anilides chemistry, Benzamides chemical synthesis, Benzamides chemistry, Dose-Response Relationship, Drug, Histone Deacetylase Inhibitors chemistry, Humans, Molecular Structure, Recombinant Proteins antagonists & inhibitors, Recombinant Proteins metabolism, Stereoisomerism, Structure-Activity Relationship, Tumor Cells, Cultured, U937 Cells, Anilides pharmacology, Benzamides pharmacology, Drug Design, Histone Deacetylase Inhibitors chemical synthesis, Histone Deacetylase Inhibitors pharmacology, Histone Deacetylases metabolism
- 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., (Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)
- Published
- 2012
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