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

  • N. P. AkentievaEmail author
  • A. R. Gizatullin
  • S. A. Goncharova
  • T. A. Raevskaya
  • N. S. Goryachev
  • N. I. Shkondina
  • T. R. Prichodchenko
  • I. V. Vystorop
  • S. S. Shushanov
ARTICLES
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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.

Keywords:

cyclic hydroxamic acids histone deacetylase inhibitors 

Notes

ACKNOWLEDGMENTS

Authors thank S.V. Blokhina, head of the nursery and vivarium of the IPCP RAS, for raising animals and methodological assistance. The work was supported by the Russian Foundation for Basic Research (project no. 13-03-01142 3.2). The work was performed as a subject of the State Program, State Registration nos. 0089-2014-0038 and 01201361874.

COMPLIANCE WITH ETHICAL STANDARDS

Conflict of interests. The authors declare that they have no conflict of interest.

Statement on the welfare of animals. All applicable international, national, and/or institutional guidelines for the care and use of animals were followed.

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Copyright information

© Pleiades Publishing, Ltd. 2019

Authors and Affiliations

  • N. P. Akentieva
    • 1
    Email author
  • A. R. Gizatullin
    • 1
  • S. A. Goncharova
    • 1
  • T. A. Raevskaya
    • 1
  • N. S. Goryachev
    • 1
  • N. I. Shkondina
    • 1
  • T. R. Prichodchenko
    • 1
  • I. V. Vystorop
    • 1
  • S. S. Shushanov
    • 2
  1. 1.Institute of Problems of Chemical Physics, Russian Academy of SciencesChernogolovkaRussia
  2. 2.Blokhin Oncological Center, Russian Ministry of HealthMoscowRussia

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