Vorinostat and Belinostat, hydroxamate-based anti-cancer agents, are nitric oxide donors

Reece G. Kenny, Ziga Ude, James R. Docherty, Celine J. Marmion

Research output: Contribution to journalArticlepeer-review

Abstract

Vorinostat (suberoylanilide hydroxamic acid; SAHA) and Belinostat are two hydroxamate-based histone deacetylase inhibitors that are used clinically as potent anti-cancer agents. Their metabolic breakdown into inactive metabolites such as carboxylic acid and glucuronic derivatives results in them having short half-lives, which can negatively impact their pharmacokinetic profiles. Herein we report the potential of both Vorinostat and Belinostat to also act as nitric oxide donors under both chemical and biological ex vivo experimental conditions. More specifically, using ruthenium(III) as an effective NO scavenger, we were able to establish, in the first instance, that both Vorinostat and Belinostat had the capacity to release NO under chemical conditions. Both Vorinostat and Belinostat were then shown to cause vascular relaxation of rat aorta via NO-mediated activation of the haem-containing guanylate cyclase enzyme. A summary of our findings is reported herein.

Original languageEnglish
Article number110981
JournalJournal of Inorganic Biochemistry
Volume206
DOIs
Publication statusPublished - May 2020

Keywords

  • Belinostat
  • Histone deacetylase inhibitors
  • Histone deacetylases
  • Nitric oxide
  • Suberoylanilide hydroxamic acid
  • Vorinostat

Fingerprint

Dive into the research topics of 'Vorinostat and Belinostat, hydroxamate-based anti-cancer agents, are nitric oxide donors'. Together they form a unique fingerprint.

Cite this