Syntheses and spectroscopic characterization of some phosphoramidates as reversible inhibitors of human acetylcholinesterase and determination of their potency

Abstract

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 (CH₃C₆H₄O-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.

Keywords::

• Ellman's method
• human acetylcholinesterase
• IC₅₀ values
• phosphoramidates
• reversible mixed inhibitors
• inhibition

Acknowledgements

We would like to express our thanks to Dr. M. Naderimanesh in the Genetics department of Tarbiat Modares University and for his helpful discussions. Also, we thank Miss. Z. Zarandi and Mrs. Kh. Khorramishad for their laboratory assistance.