title: Synthesis and inhibitory activity of ureidophosphonates, against acetylcholinesterase: pharmacological assay and molecular modeling.
abstract: A novel method has been developed for the synthesis of 1-ureidophosphonates through a three components condensation of aldehyde with amine and diethylphosphite in the presence of sulfanilic acid as catalyst followed by subsequent reaction of the product with isocyanate. This method is easy, rapid, and good yielding. The anticholinesterase (AChE) activities (inhibition potency through IC(50)) of newly synthesized 1-ureidophosphonates were also investigated. The activities of the synthesized compounds toward the enzyme AChE were determined and compared in terms of their molecular structures and it was found, through molecular docking simulations, that the most potent derivative (compound 3i) inhibited the enzyme through binding to the peripheral anionic site (PAS) and not to its acylation site (A site).
authors.affiliation: Department of Chemistry, Institute for Advanced Studies in Basic Sciences (IASBS), Gava Zang, Zanjan 45137-66731, Iran. kaboudin@iasbs.ac.ir
authors.forename: Babak
authors.initials: B
authors.lastname: Kaboudin
authors.forename: Marzban
authors.initials: M
authors.lastname: Arefi
authors.forename: Saeed
authors.initials: S
authors.lastname: Emadi
authors.forename: Vahid
authors.initials: V
authors.lastname: Sheikh-Hasani
mesh_terms: D000110:Acetylcholinesterase / Q000737:chemistry* / Q000378:metabolism; D000447:Aldehydes / Q000737:chemistry; D000588:Amines / Q000737:chemistry; D001665:Binding Sites; D002800:Cholinesterase Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D003198:Computer Simulation; D006801:Humans; D008958:Models, Molecular; D019636:Neurodegenerative Diseases / Q000188:drug therapy / Q000201:enzymology; D063065:Organophosphonates / Q000138:chemical synthesis* / Q000494:pharmacology; D017905:Phosphites / Q000737:chemistry; D011485:Protein Binding; D013329:Structure-Activity Relationship; D013425:Sulfanilic Acids / Q000737:chemistry
chemical_list: D000447:Aldehydes; D000588:Amines; D002800:Cholinesterase Inhibitors; D063065:Organophosphonates; D017905:Phosphites; D013425:Sulfanilic Acids; D000110:Acetylcholinesterase