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

Raffaella Cincinelli, Loana Musso, Giuseppe Giannini, Valentina Zuco, Michelandrea De Cesare, Franco Zunino, Sabrina Dallavalle

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)251-259
Number of pages9
JournalEuropean Journal of Medicinal Chemistry
Volume79
DOIs
Publication statusPublished - May 22 2014

Keywords

  • Adamantyl moiety
  • Antiproliferative activity
  • HDAC inhibitors
  • Hydroxamic acids

ASJC Scopus subject areas

  • Drug Discovery
  • Organic Chemistry
  • Pharmacology
  • Medicine(all)

Fingerprint Dive into the research topics of 'Influence of the adamantyl moiety on the activity of biphenylacrylohydroxamic acid-based HDAC inhibitors'. Together they form a unique fingerprint.

Cite this