Anticancer Activity of Spirocyclic Hydroxamic Acids (Derivatives of 1-Hydroxy-1,4,8-Triazaspiro[4,5]Decan-2-One), Histone Deacetylase Inhibitors

Abstract

The effect of 10 racemic spirocyclic hydroxamic acids (CHA 1–10, derivatives of 1-hydroxy-1,4,8-triazaspiro[4,5]decan-2-one), containing pharmacophore imidazolidinone and piperidine fragments with different substituents, on the activity of enzyme histone deacetylase (HDAC) was studied. It was shown that CHA (1–10) inhibit HDAC activity in cultured breast cancer cells. It was shown that CHA (1–10) as a part of polychemotherapy with cisplatin and cyclophosphane have a pronounced chemosensitizing antitumor activity in vivo. The results obtained on tumor models in vivo showed that CHA can be considered as potential medicinal components of tumor polychemotherapy.