title: Molecular perception of interactions between bis(7)tacrine and cystamine-tacrine dimer with cholinesterases as the promising proposed agents for the treatment of Alzheimer's disease.
abstract: The infamous chronic neurodegenerative disease, Alzheimer's, that starts with short-term memory loss and eventually leads to gradual bodily function decline which has been attributed to the deficiency in brain neurotransmitters, acetylcholine, and butylcholine. As a matter of fact, design of compounds that can inhibit cholinesterases activities (acetylcholinesterase and butylcholinesterase) has been introduced as an efficient method to treat Alzheimer's. Among proposed compounds, bis(7)tacrine (B7T) is recognized as a noteworthy suppressor for Alzheimer's disease. Recently a new analog of B7T, cystamine-tacrine dimer is offered as an agent to detain Alzheimer's complications, even better than the parent compound. In this study, classical molecular dynamic simulations have been employed to take a closer look into the modes of interactions between the mentioned ligands and both cholinesterase enzymes. According to our obtained results, the structural differences in the target enzymes active sites result in different modes of interactions and inhibition potencies of the ligands against both enzymes. The obtained information can help to investigate those favorable fragments in the studied ligands skeletons that have raised the potency of the analog in comparison with the parent compound to design more potent multi target ligands to heal Alzheimer's disease.
authors.affiliation: a Molecular Simulation Research Laboratory, Department of Chemistry , Iran University of Science & Technology , Tehran , Iran.
authors.forename: Mahboobeh
authors.initials: M
authors.lastname: Eslami
authors.affiliation: a Molecular Simulation Research Laboratory, Department of Chemistry , Iran University of Science & Technology , Tehran , Iran.
authors.forename: Seyed Majid
authors.initials: SM
authors.lastname: Hashemianzadeh
authors.affiliation: b Faculty of Pharmacy and Medicinal Plants Research Center, Department of Medicinal Chemistry , Tehran University of Medical Sciences , Tehran , Iran.
authors.forename: Kowsar
authors.initials: K
authors.lastname: Bagherzadeh
authors.affiliation: a Molecular Simulation Research Laboratory, Department of Chemistry , Iran University of Science & Technology , Tehran , Iran.
authors.forename: Seyed Abolfazl
authors.initials: SA
authors.lastname: Seyed Sajadi
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy; D001665:Binding Sites; D020134:Catalytic Domain; D002800:Cholinesterase Inhibitors / Q000737:chemistry* / Q000494:pharmacology; D002802:Cholinesterases / Q000737:chemistry*; D003538:Cystamine / Q000737:chemistry*; D006801:Humans; D006860:Hydrogen Bonding; D008024:Ligands; D008958:Models, Molecular; D008968:Molecular Conformation; D062105:Molecular Docking Simulation; D056004:Molecular Dynamics Simulation; D011485:Protein Binding; D013329:Structure-Activity Relationship; D013619:Tacrine / Q000031:analogs & derivatives* / Q000737:chemistry
chemical_list: C122128:1,7-N-heptylene-bis-9,9'-amino-1,2,3,4-tetrahydroacridine; D002800:Cholinesterase Inhibitors; D008024:Ligands; D013619:Tacrine; D002802:Cholinesterases; D003538:Cystamine
keywords: Alzheimer’s disease; acetylcholinesterase; butyrylcholinesterase; classical molecular dynamic simulations; multitarget-directed ligands