New bis-hydantoin/thiohydantoin derivatives: Regioselective synthesis, antibacterial activity, molecular docking, and computational insights

Concerning the reported biological activities of bis-heterocycles, hydantoin, and thiohydantoin moieties, a series of some new bis-hydantoins/thiohydantoins have been prepared, characterized, and screened for their antimicrobial properties. The regioselectivity of the synthetic reactions was discussed and chemical structures of products were elucidated using spectroscopic techniques in addition to elemental analysis. DFT calculations with the IEF-PCM model, to mimic the implicit solvation, have been performed to study the mechanism of reaction as well as the molecular structures and the relative stabilities of the synthesized compounds. The antimicrobial results show that some bis-hydantoin compounds exhibited high antibacterial response against Staphylococcus aureus, Enterococcus faecalis, Escherichia coli, and Pseudomonas aeruginosa. The inhibitory activity of synthesized compounds may be due to the hydrogen acceptor/donor (HAD) behavior of substituted function groups like thiocarbonyl, carbonyl, acetyl, NH, and OH. The synthetic potential and antimicrobial activities of all compounds under investigation were confirmed using molecular docking simulation into the active sites of different kinds of proteins.