Design, synthesis, and computational explorations of novel 2‐thiohydantoin nucleosides with cytotoxic activities

Abstract

A novel series of S-alkylated, N-alkylated, and N-glycosylated 2-thiohydantoin derivatives were synthesized via the reaction of (E)-5-(arylidene)-1-phenyl-2-thiohydantoins 5a-d with alkyl halides/glycosyl bromides under aqueous, anhydrous alkaline/glycosylation conditions, respectively. The structures of the novel compounds were confirmed by elemental analyses and spectral data. Computational studies using DFT calculations with B3LYP/6-31 + G (d,p) level were performed to study the electronic and geometric properties obtained from the stable structure of the investigated compounds. A good correlation was found between the quantum chemical parameters and experimental observations. The synthesized derivatives exhibited good binding interactions towards the cyclin-dependent kinase 2, especially (E)-5-(chlorobenzylidene)-3-(2 0 0.3 0 0.4 0 0.6 0 -tetra-O-acetyl-β-D-galactopyranosyl)-1-phenyl-2-thiohydantoin (11g), which have good key interactions such as the co-crystallized ligand. In addition, it had selective cytotoxic activities with IC 50 = 12.4 μM against lung cancer A549 cells.

Design, Synthesis, Computational Investigations, and Antitumor Evaluation ofN-Rhodanine Glycosides Derivatives as Potent DNA Intercalation and Topo II Inhibition against Cancer Cells

“…Despite these activities, research into anticancer drugs from this class that have less side effects while still being effective is still in its infancy. Previous investigations of structurally similar heterocyclic system glycosyl derivatives were published. − …”