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

Abstract EN

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.