Study of novel triazolo-benzodiazepine analogues as antidepressants targeting by molecular docking and ADMET properties prediction
Assia Belhassan,
Hanane Zaki,
Mohamed Benlyas,
Tahar Lakhlifi,
Mohammed Bouachrine
Affiliations
Assia Belhassan
MCNS Laboratory, Faculty of Science, Moulay Ismail University, Meknes, Morocco; Materials, Environment & Modeling Laboratory, High School of Technology, Moulay Ismail University, Meknes, Morocco
Hanane Zaki
Materials, Environment & Modeling Laboratory, High School of Technology, Moulay Ismail University, Meknes, Morocco; Biology Environment and Health Laboratory, Faculty of Science and Technics, Moulay Ismail University, Errachdia, Morocco
Mohamed Benlyas
Biology Environment and Health Laboratory, Faculty of Science and Technics, Moulay Ismail University, Errachdia, Morocco
Tahar Lakhlifi
MCNS Laboratory, Faculty of Science, Moulay Ismail University, Meknes, Morocco
Mohammed Bouachrine
MCNS Laboratory, Faculty of Science, Moulay Ismail University, Meknes, Morocco; Materials, Environment & Modeling Laboratory, High School of Technology, Moulay Ismail University, Meknes, Morocco; Corresponding author.
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: M1, M2, M3 and M11 showed less toxicity than the other studied molecules against algae, for daphnia the molecules M1, M2, M3, M8, M10 and M11 showed less toxicity than the reference molecule (Nortriptyline).
