1. Synthesis, isomerization and biological activity of novel 2-selenohydantoin derivatives.
- Author
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Ivanenkov YA, Veselov MS, Rezekin IG, Skvortsov DA, Sandulenko YB, Polyakova MV, Bezrukov DS, Vasilevsky SV, Kukushkin ME, Moiseeva AA, Finko AV, Koteliansky VE, Klyachko NL, Filatova LA, Beloglazkina EK, Zyk NV, and Majouga AG
- Subjects
- Antineoplastic Agents pharmacology, Antioxidants pharmacology, Azoles pharmacology, Cell Line, Tumor, Cell Survival drug effects, Copper chemistry, Cyanates chemistry, Drug Screening Assays, Antitumor, Glutathione Peroxidase antagonists & inhibitors, Glutathione Peroxidase chemistry, Humans, Hydantoins pharmacology, Inhibitory Concentration 50, Isoindoles, Organoselenium Compounds pharmacology, Pyridines chemistry, Quantum Theory, Stereoisomerism, Structure-Activity Relationship, Antineoplastic Agents chemical synthesis, Antioxidants chemical synthesis, Hydantoins chemical synthesis, Organoselenium Compounds chemical synthesis
- 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 ZāE 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., (Copyright © 2016 Elsevier Ltd. All rights reserved.)
- Published
- 2016
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