Synthesis and inhibitory activity of ureidophosphonates, against acetylcholinesterase: Pharmacological assay and molecular modeling

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 IC50) 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).

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. The compounds were evaluated for their acetylcholinesterase (AChE) inhibition potency through IC50 determination.Figure optionsDownload as PowerPoint slideHighlights
► Novel method for the synthesis of 1-ureidophosphonates.
► Acetylcholinesterase (AChE) inhibition potency.
► IC50 determination.
► Molecular modeling studies.
► Peripheral site of AChE.