Synthesis, isomerization and biological activity of novel 2-selenohydantoin derivatives. Issue 4 (15th February 2016)

• Record Type: Journal Article
• Authors: Ivanenkov, Yan A.; Veselov, Mark S.; Rezekin, Igor G.; Skvortsov, Dmitriy A.; Sandulenko, Yuri B.; Polyakova, Marina V.; Bezrukov, Dmitry S.; Vasilevsky, Sergey V.; Kukushkin, Maxim E.; Moiseeva, Anna A.; Finko, Alexander V.; Koteliansky, Victor E.; Klyachko, Natalia L.; Filatova, Lubov A.; Beloglazkina, Elena K.; Zyk, Nikolay V.; Majouga, Alexander G.
• Is Part Of: Bioorganic & medicinal chemistry. Volume 24:Issue 4(2016)
• Page Start: 802
• Page End: 811
• Publication Date: 2016-02-15
• Subjects: Selenohydantoin -- Isomerization -- Complexation -- Anticancer activity -- Antioxidant activity -- Electrochemistry -- Quantum-chemical study; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; Biochemistry -- Periodicals; Chemistry, Clinical -- Periodicals; Chemistry, Organic -- Periodicals; Chimie bio-organique -- Périodiques; Chimie pharmaceutique -- Périodiques; 615.19
• DOI: 10.1016/j.bmc.2015.12.050
• Languages: English
• ISSNs: 0968-0896

Abstract

Graphical abstract: 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 Cu 2+ cations. The detailed mechanism of this transformation was suggested on the basis of quantum-chemical calculations, and the key role of Cu 2+ 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.