Design, synthesis, and biological evaluation of 2-aminobenzanilide derivatives as potent and selective HDAC inhibitors |
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Authors: | Stolfa Diana A Stefanachi Angela Gajer Julia M Nebbioso Angela Altucci Lucia Cellamare Saverio Jung Manfred Carotti Angelo |
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Affiliation: | 1. Institute of Pharmaceutical Sciences, Albert‐Ludwigs‐Universit?t Freiburg, Albertstr. 25, 79104 Freiburg (Germany);2. Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Università degli Studi di Bari “A. Moro”, Via Orabona 4, 70125 Bari (Italy);3. Department of General Pathology, Seconda Università di Napoli, Vico L. De Crecchio 7, 80138 Napoli (Italy);4. CNR‐IGB “ABT”, Via P. Castellino 111, 80131 Napoli (Italy) |
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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. |
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Keywords: | 2‐aminobenzanilide cancer histone deacetylases inhibitors ZBGs |
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