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Scientific article
English

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

Published inEuropean journal of medicinal chemistry, vol. 112, p. 99-105
Publication date2016
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.

Keywords
  • Antineoplastic Agents/chemistry/pharmacology
  • Apoptosis/drug effects
  • Biphenyl Compounds/chemistry/pharmacology
  • Colonic Neoplasms/drug therapy/metabolism
  • Drug Screening Assays
  • Antitumor
  • HCT116 Cells
  • Histone Deacetylase Inhibitors/chemistry/pharmacology
  • Histone Deacetylases/metabolism
  • Humans
  • Hydroxamic Acids/chemistry/pharmacology
  • Molecular Docking Simulation
  • Neoplasms/drug therapy/metabolism
  • Structure-Activity Relationship
Citation (ISO format)
CINCINELLI, Raffaella et al. Biphenyl-4-yl-acrylohydroxamic acids: Identification of a novel indolyl-substituted HDAC inhibitor with antitumor activity. In: European journal of medicinal chemistry, 2016, vol. 112, p. 99–105. doi: 10.1016/j.ejmech.2016.02.001
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Article (Published version)
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ISSN of the journal0223-5234
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