Synthesis and comparison of the biological activity of monocyclic phosphonate, difluorophosphonate and phosphate analogs of the natural AChE inhibitor cyclophostin

Benjamin P Martin; Elena Vasilieva; Cynthia M Dupureur; Christopher D Spilling

doi:10.1016/j.bmc.2015.10.044

Synthesis and comparison of the biological activity of monocyclic phosphonate, difluorophosphonate and phosphate analogs of the natural AChE inhibitor cyclophostin

Bioorg Med Chem. 2015 Dec 15;23(24):7529-34. doi: 10.1016/j.bmc.2015.10.044. Epub 2015 Oct 30.

Authors

Benjamin P Martin¹, Elena Vasilieva¹, Cynthia M Dupureur¹, Christopher D Spilling²

Affiliations

¹ Department of Chemistry and Biochemistry and the Center for Nanoscience, University of Missouri-St. Louis, One University Boulevard, St. Louis, MO 63121, USA.
² Department of Chemistry and Biochemistry and the Center for Nanoscience, University of Missouri-St. Louis, One University Boulevard, St. Louis, MO 63121, USA. Electronic address: cspill@umsl.edu.

PMID: 26585276
DOI: 10.1016/j.bmc.2015.10.044

Abstract

New monocyclic phosphate, phosphonate and difluorophosphonate analogs of the natural AChE inhibitor cyclophostin were synthesized and their activity toward human AChE examined. Surprisingly, the phosphate, phosphonate, and difluorophosphonate analogs all showed diminished activity when compared with the natural product.

Keywords: Acetyl cholinesterase; Cyclic phosphate; Cyclic phosphonate; Difluorophosphonate; Inhibition.

MeSH terms

Acetylcholinesterase / metabolism
Cholinesterase Inhibitors / chemical synthesis
Cholinesterase Inhibitors / chemistry*
Cholinesterase Inhibitors / pharmacology*
Halogenation
Humans
Organophosphates / chemical synthesis
Organophosphates / chemistry
Organophosphates / pharmacology
Organophosphonates / chemical synthesis
Organophosphonates / chemistry
Organophosphonates / pharmacology
Organophosphorus Compounds / chemical synthesis
Organophosphorus Compounds / chemistry*
Organophosphorus Compounds / pharmacology*

Substances

Cholinesterase Inhibitors
Organophosphates
Organophosphonates
Organophosphorus Compounds
cyclophostin
Acetylcholinesterase