Synthesis, isomerization and biological activity of novel 2-selenohydantoin derivatives

Yan A. Ivanenkov, Mark S. Veselov, Igor G. Rezekin, Dmitriy A. Skvortsov, Yuri B. Sandulenko, Marina V. Polyakova, Dmitry S. Bezrukov, Sergey V. Vasilevsky, Maxim E. Kukushkin, Anna A. Moiseeva, Alexander V. Finko, Victor E. Koteliansky, Natalia L. Klyachko, Lubov A. Filatova, Elena K. Beloglazkina, Nikolay V. Zyk, Alexander G. Majouga

Research output: Contribution to journalArticlepeer-review

22 Citations (Scopus)

Abstract

A set of novel selenohydantoins were synthesized via a convenient and versatile approach involving the reaction of isoselenocyanates with various amines. We also revealed an unexpected Z→E isomerization of pyridin-2-yl-substituted selenohydantoins in the presence of Cu2+ cations. The detailed mechanism of this transformation was suggested on the basis of quantum-chemical calculations, and the key role of Cu2+ was elucidated. The obtained compounds were subsequently evaluated against a panel of different cancer cell lines. As a result, several molecules were identified as promising micromolar hits with good selectivity index. Instead of analogous thiohydantoins, which have been synthesized previously, selenohydantoins demonstrated a relatively high antioxidant activity comparable (or greater) to the reference molecule, Ebselen, a clinically approved drug candidate. The most active compounds have been selected for further biological trials.

Original languageEnglish
Pages (from-to)802-811
Number of pages10
JournalBioorganic and Medicinal Chemistry
Volume24
Issue number4
DOIs
Publication statusPublished - 15 Feb 2016
Externally publishedYes

Keywords

  • Anticancer activity
  • Antioxidant activity
  • Complexation
  • Electrochemistry
  • Isomerization
  • Quantum-chemical study
  • Selenohydantoin

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