Study of novel triazolo-benzodiazepine analogues as antidepressants targeting by molecular docking and ADMET properties prediction

In this study, we have selected a series of a new family of molecules bearing Triazolo-benzodiazepines, an eleven membered heterocyclic ring has been studied for antidepression activity. Docking studies suggested that all the eleven ligands interacted well within active site of Drosophila melanogaster dopamine transporter (dDAT) (PDB ID: 4M48). Most ligands formed H-bond with amino acid Phe43, Asp46, Asp475, Tyr123, Ser421 and/or Gln316 and also exhibited Pi and Pi-Pi interactions with amino acid residues Tyr124, Phe319, Phe43, Phe325, Ala479 and Val120. In silico ADME evaluations of compounds showed more than 96% intestinal absorption for all compounds. During in vitro Toxicity properties prediction, the Triazolo-benzodiazepines derivatives: M-1, M-2, M-3 and M-11 showed less toxicity than the other studied molecules against algae, for daphnia the molecules M-1, M-2, M-3, M-8, M-10 and M-11 showed less toxicity than the reference molecule (Nortriptyline).