Synthesis and biological evaluation of the first example of NO-donor histone deacetylase inhibitor

Emily Borretto, Loretta Lazzarato, Francesco Spallotta, Chiara Cencioni, Yuri D'Alessandra, Carlo Gaetano, Roberta Fruttero, Alberto Gasco

Research output: Contribution to journalArticle

Abstract

The NO-donor histone deacetylase inhibitor 2, formally obtained by joining Entinostat 1, a moderately selective Class I histone deacetylases (HDACs) inhibitor, to a 4-(methylaminomethyl)furoxan-3-carbonitrile scaffold, is described and its preliminary biological profile discussed. This hybrid regulates Classes I and II HDACs. Nitric oxide (NO) released by the compound activates soluble guanylate cyclase (sGC), causing Class II nuclear shuttling and chromatin modifications, with consequences on gene expression. The hybrid affects a number of micro-RNAs not modulated by its individual components; it promotes myogenic differentiation, inducing the formation of larger myotubes with significantly more nuclei per fiber, in a more efficient manner than the 1:1 mixture of its two components. The hybrid is an example of a new class of NO-donor HDACs now being developed, which should be of interest for treating a number of diseases.

Original languageEnglish
Pages (from-to)994-999
Number of pages6
JournalACS Medicinal Chemistry Letters
Volume4
Issue number10
DOIs
Publication statusPublished - Oct 10 2013

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Keywords

  • epigenetics
  • HDAC
  • histone deacetylase inhibitors
  • multitarget drugs
  • NO-donor

ASJC Scopus subject areas

  • Organic Chemistry
  • Drug Discovery
  • Biochemistry

Cite this

Borretto, E., Lazzarato, L., Spallotta, F., Cencioni, C., D'Alessandra, Y., Gaetano, C., Fruttero, R., & Gasco, A. (2013). Synthesis and biological evaluation of the first example of NO-donor histone deacetylase inhibitor. ACS Medicinal Chemistry Letters, 4(10), 994-999. https://doi.org/10.1021/ml400289e