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Design, Synthesis, and Biological Evaluation of 2‐Aminobenzanilide Derivatives as Potent and Selective HDAC Inhibitors
Author(s) -
Stolfa Diana A.,
Stefanachi Angela,
Gajer Julia M.,
Nebbioso Angela,
Altucci Lucia,
Cellamare Saverio,
Jung Manfred,
Carotti Angelo
Publication year - 2012
Publication title -
chemmedchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.817
H-Index - 100
eISSN - 1860-7187
pISSN - 1860-7179
DOI - 10.1002/cmdc.201200193
Subject(s) - epigenetics , histone , chemistry , enzyme , histone deacetylase , biochemistry , biology , computational biology , gene , cancer research
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.