Alkynyl and β-ketophosphonates: Selective and potent butyrylcholinesterase inhibitors

CAVALLARO, VALERIA; MOGLIE, YANINA F.; MURRAY, ANA P.; RADIVOY, GABRIEL E.

BIOORGANIC CHEMISTRY

ACADEMIC PRESS INC ELSEVIER SCIENCE

Año: 2018 vol. 77 p. 420 - 428

0045-2068

A series of thirty-three alkynyl and β-ketophosphonates were evaluated for their in vitro acetyl- and butyryl-cholinesterase (AChE and BChE) inhibitory activities using Ellman´s spectrophotometric method. None of the examined compounds inhibited AChE activity at tested concentrations while twenty-nine of them showed significant and selective inhibition of BChE with IC50 values between 38.60 µM and 0.04 µM. In addition, structure-activity relationships were discussed. The most effective inhibitors were the dibutyl o-methoxyphenyl alkynylphosphonate 3dc and dibutyl o-methoxyphenyl β-ketophosphonate 4dc. Activities of most potent compounds were also compared with a commercial organophosphorus compound. These results could inspire the design of new inhibitors with stronger activity against BChE.