2. Academic Validation
  3. Influence of the adamantyl moiety on the activity of biphenylacrylohydroxamic acid-based HDAC inhibitors

Influence of the adamantyl moiety on the activity of biphenylacrylohydroxamic acid-based HDAC inhibitors

  • Eur J Med Chem. 2014 May 22:79:251-9. doi: 10.1016/j.ejmech.2014.04.021.
Raffaella Cincinelli 1,  Loana Musso 1,  Giuseppe Giannini 2,  Valentina Zuco 3,  Michelandrea De Cesare 3,  Franco Zunino 3,  Sabrina Dallavalle 4
Affiliations

Affiliations

  • 1 Department of Food, Environmental and Nutritional Sciences, Division of Chemistry and Molecular Biology, Università di Milano, Via Celoria 2, 20133 Milano, Italy.
  • 2 R&D Sigma-Tau Industrie Farmaceutiche Riunite S.p.A., Via Pontina Km 30,400, I-00040 Pomezia, RM, Italy.
  • 3 Molecular Pharmacology Unit, Dept. Experimental Oncology and Molecular Medicine, Fondazione IRCCS Istituto Nazionale Tumori, Via Amadeo 42, I-20133 Milan, Italy.
  • 4 Department of Food, Environmental and Nutritional Sciences, Division of Chemistry and Molecular Biology, Università di Milano, Via Celoria 2, 20133 Milano, Italy. Electronic address: sabrina.dallavalle@unimi.it.
PMID: 24742384 DOI: 10.1016/j.ejmech.2014.04.021
Abstract

To investigate the influence of the adamantyl group on the biological properties of known HDAC inhibitors with a 4-phenylcinnamic skeleton, a series of compounds having the adamantyl moiety in the cap structure were synthesized and compared to the corresponding hydroxamic acids lacking this group. An unexpected finding was the substantial reduction of inhibitory activity toward the tested Enzymes, in particular HDAC6, following the introduction of the adamantyl group. In spite of the reduced ability to function as HDAC inhibitors, the compounds containing the adamantyl moiety still retained a good efficacy as antiproliferative and proapoptotic agents. A selected compound (2c; ST3056) of this series exhibited an appreciable antitumor activity against the colon carcinoma xenograft HCT116.

Keywords

Adamantyl moiety; Antiproliferative activity; HDAC inhibitors; Hydroxamic acids.

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