Abstract
Objective: The purpose of this study was to synthesize three new derivatives of
metoclopramide by diazotization and replacement reactions and then to quantify in
vitro their protection effects on blood cholinesterases using chlorpyrifos as a potent
inhibitor.
methods: The three new metoclopramide derivatives were synthesized via
Sandmeyer reaction, the chemical structures of these derivatives were identified by
physico-chemical and spectroscopic (U.V. and FTIR) techniques.
Results and conclusion: The results of in vitro evaluation of their human
cholinesterases inhibition and protection against chlorpyrifos indicated that the (OH)
functional group binds to cholinesterase (ChE) at the same organophosphorous (OP)
binding site and shows some competition and protection ability but not to a significant
degree, while the (Cl and I) functional groups bind to the ChE at site differs from OP
binding site, as well as the (I) functional group has more selectivity for enzyme
moiety and binds more strongly than the (Cl) group, so that shows more ChE
inhibiting ability
