Modification of the cap group of biphenylacrylohydroxamic acid-based HDAC inhibitors led to the identification of a new derivative (3) characterized by an indolyl-substituted 4-phenylcinnamic skeleton. Molecular docking was used to predict the optimal conformation in the class I HDACs active site. Compound 3 showed HDAC inhibitory activity and antiproliferative activity against a panel of tumor cell lines, in the low μM range. The compound was further tested in vitro for acetylation of histone H4 and other non-histone proteins, and in vivo in a colon carcinoma model, showing significant proapoptotic and antitumor activities.
Biphenyl-4-yl-acrylohydroxamic acids: identification of a novel indolyl-substituted HDAC inhibitor with antitumor activity / R. Cincinelli, V. Zwick, L. Musso, V. Zuco, M. De Cesare, F. Zunino, C. Simoes Pires, A. Nurisso, G. Giannini, M. Cuendet, S. Dallavalle. - In: EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY. - ISSN 0223-5234. - 112(2016 Apr 13), pp. 99-105.
|Titolo:||Biphenyl-4-yl-acrylohydroxamic acids: identification of a novel indolyl-substituted HDAC inhibitor with antitumor activity|
CINCINELLI, RAFFAELLA (Primo)
DALLAVALLE, SABRINA (Ultimo)
|Parole Chiave:||Hydroxamic acids; HDAC inhibitors; Antiproliferative activity; Antitumor activity; Synthesis|
|Settore Scientifico Disciplinare:||Settore CHIM/08 - Chimica Farmaceutica|
Settore CHIM/06 - Chimica Organica
|Data di pubblicazione:||13-apr-2016|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1016/j.ejmech.2016.02.001|
|Appare nelle tipologie:||01 - Articolo su periodico|