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.
Influence of the adamantyl moiety on the activity of biphenylacrylohydroxamic acid-based HDAC inhibitors / R. Cincinelli, L. Musso, G. Giannini, V. Zuco, M. De Cesare, F. Zunino, S. Dallavalle. - In: EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY. - ISSN 0223-5234. - 79(2014), pp. 251-259.
|Titolo:||Influence of the adamantyl moiety on the activity of biphenylacrylohydroxamic acid-based HDAC inhibitors|
DALLAVALLE, SABRINA (Corresponding)
|Parole Chiave:||Adamantyl moiety; Hydroxamic acids; HDAC inhibitors; Antiproliferative activity|
|Settore Scientifico Disciplinare:||Settore CHIM/06 - Chimica Organica|
Settore CHIM/08 - Chimica Farmaceutica
|Progetto:||Progettazione e Sintesi di Antitumorali da Prodotti Naturali: Composti Interagenti con Tubulina e Topoisomerasi|
|Data di pubblicazione:||2014|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1016/j.ejmech.2014.04.021|
|Appare nelle tipologie:||01 - Articolo su periodico|