New hybrids based on benzimidazole and diazepine moieties: design, synthesis, characterization, molecular docking...

Benzodiazepines are one of the most widely prescribed pharmacologic agents in the world. They are employed for numerous indications, including anxiety, insomnia, muscle relaxation, relief from spasticity caused by central nervous system pathology and epilepsy. In this work, we have synthesized some new hybrids based on benzimidazole and diazepine scaffolds from the reaction of suitable benzimidazole derivatives with glycine. NMR spectra, IR and mass as well as elemental analyses approved the structure of the title compounds. In vitro interactions of the title compounds were also examined on recombinant benzodiazepine receptors (αxβ2/3γ2, x = 1-3, 5) expressed in HEK293 cells. The results indicated that the title compounds exhibited suitable affinity for α1β2 γ2 subtype (K_i = 16-29 nM). To achieve deeper insight into their interactions with benzodiazepine receptors, molecular dynamics simulation was employed. According to the results obtained from the molecular dynamics simulation, Pro85, Leu103, Pro101, Gln102, Ile79, Ser80, Pro17, Leu82 and Val84 interact with the most potent ligand by hydrophobic interactions and Asp86 and Leu87 interact with the ligand by hydrogen bond interactions.Communicated by Ramaswamy H. Sarma.