Synthesis, isomerization and biological activity of novel 2 selenohydantoin derivatives.
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.
Bioorganic medicinal chemistry