Synthesis of new metoclopramide derivatives and in vitro evaluation of their human cholinesterases protection against Chlorpyrifos


Objective: The purpose of this study was to synthesize three new derivatives ofmetoclopramide by diazotization and replacement reactions and then to quantify invitro their protection effects on blood cholinesterases using chlorpyrifos as a potentinhibitor.methods: The three new metoclopramide derivatives were synthesized viaSandmeyer reaction, the chemical structures of these derivatives were identified byphysico-chemical and spectroscopic (U.V. and FTIR) techniques.Results and conclusion: The results of in vitro evaluation of their humancholinesterases 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 significantdegree, while the (Cl and I) functional groups bind to the ChE at site differs from OPbinding site, as well as the (I) functional group has more selectivity for enzymemoiety and binds more strongly than the (Cl) group, so that shows more ChEinhibiting ability