Identification of histone deacetylase inhibitors with (arylidene)aminoxy scaffold active in uveal melanoma cell lines

Susanna Nencetti, Doretta Cuffaro, Elisa Nuti, Lidia Ciccone, Armando Rossello, Marina Fabbi, Flavio Ballante, Gabriella Ortore, Grazia Carbotti, Francesco Campelli, Irene Banti, Rosaria Gangemi, Garland R. Marshall, Elisabetta Orlandini

Research output: Contribution to journalArticlepeer-review

Abstract

Uveal melanoma (UM) represents an aggressive type of cancer and currently, there is no effective treatment for this metastatic disease. In the last years, histone deacetylase inhibitors (HDACIs) have been studied as a possible therapeutic treatment for UM, alone or in association with other chemotherapeutic agents. Here we synthesised a series of new HDACIs based on the SAHA scaffold bearing an (arylidene)aminoxy moiety. Their HDAC inhibitory activity was evaluated on isolated human HDAC1, 3, 6, and 8 by fluorometric assay and their binding mode in the catalytic site of HDACs was studied by molecular docking. The most promising hit was the quinoline derivative VS13, a nanomolar inhibitor of HDAC6, which exhibited a good antiproliferative effect on UM cell lines at micromolar concentration and a capability to modify the mRNA levels of HDAC target genes similar to that of SAHA.

Original languageEnglish
Pages (from-to)34-47
Number of pages14
JournalJournal of Enzyme Inhibition and Medicinal Chemistry
Volume36
Issue number1
DOIs
Publication statusPublished - Jan 1 2021

Keywords

  • (arylidene)aminoxy-based hydroxamates
  • HDAC inhibitors
  • HDAC6
  • SAHA
  • Uveal melanoma

ASJC Scopus subject areas

  • Pharmacology
  • Drug Discovery

Fingerprint Dive into the research topics of 'Identification of histone deacetylase inhibitors with (arylidene)aminoxy scaffold active in uveal melanoma cell lines'. Together they form a unique fingerprint.

Cite this