Syntheses and spectroscopic characterization of some phosphoramidates as reversible inhibitors of human acetylcholinesterase and determination of their potency.
The ability of phosphoramidates Me2NP(O)(Cl)(p-NHC6H4NO2) 1, Me2NP(O)(p-NHC6H4NO2)2 2, (CH3C6H4O-p)P(O)(p-NHC6H4NO2)2 3 and (CH3C6H40-p)2P(O)(p-NHC6H4NO2) 4 to inhibit human acetylcholinesterase (hAChE) has been evaluated by a modified Ellman's method and spectrophotometric measurements. Results showed that compounds 1 and 2 do not have any inhibitory potency, whereas compounds 3 and 4 were reversible mixed inhibitors. The IC50 values for inhibitors 3 and 4 were 0.143 and 0.581 mM, respectively. The previously unknown compounds 3 and 4 were synthesized and characterized by 1H, 13C, 31P NMR and IR spectroscopy and elemental analysis.
Department of Chemistry, Tarbiat Modarres University, Tehran, Iran. gholi_kh@modares.ac.ir
Khodayar
K
Gholivand
Zahra
Z
Shariatinia
Khosro
K
Khajeh
Hossein
H
Naderimanesh
D000110:Acetylcholinesterase / Q000737:chemistry* / Q000378:metabolism; D000577:Amides / Q000138:chemical synthesis* / Q000737:chemistry* / Q000494:pharmacology; D002800:Cholinesterase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry* / Q000494:pharmacology; D006801:Humans; D020128:Inhibitory Concentration 50; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D010756:Phosphoric Acids / Q000138:chemical synthesis* / Q000737:chemistry* / Q000494:pharmacology; D013055:Spectrophotometry, Infrared; D013329:Structure-Activity Relationship
D000577:Amides; D002800:Cholinesterase Inhibitors; D010756:Phosphoric Acids; C011067:phosphoramidic acid; D000110:Acetylcholinesterase