Biphenyl-4-yl-acrylohydroxamic acids: Identification of a novel indolyl-substituted HDAC inhibitor with antitumor activity

Raffaella Cincinelli, Vincent Zwick, Loana Musso, Valentina Zuco, Michelandrea De Cesare, Franco Zunino, Claudia Simoes-Pires, Alessandra Nurisso, Giuseppe Giannini, Muriel Cuendet, Sabrina Dallavalle

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
Pages (from-to)99-105
Number of pages7
JournalEuropean Journal of Medicinal Chemistry
Volume112
DOIs
Publication statusPublished - 2016

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Keywords

  • Antiproliferative activity
  • Antitumor activity
  • HDAC inhibitors
  • Hydroxamic acids
  • Synthesis

ASJC Scopus subject areas

  • Pharmacology
  • Drug Discovery
  • Organic Chemistry

Cite this

Cincinelli, R., Zwick, V., Musso, L., Zuco, V., De Cesare, M., Zunino, F., Simoes-Pires, C., Nurisso, A., Giannini, G., Cuendet, M., & Dallavalle, S. (2016). Biphenyl-4-yl-acrylohydroxamic acids: Identification of a novel indolyl-substituted HDAC inhibitor with antitumor activity. European Journal of Medicinal Chemistry, 112, 99-105. https://doi.org/10.1016/j.ejmech.2016.02.001