4-Hydroxybenzohydrazide: A Potential Reactivator for Malathion-Inhibited Human Acetylcholinesterase

Abstract

Abstract For years, oximes are used as antidotes for organophosphate (OP) poisoning treatments. However, due to the limitations of oxime therapy, the discovery of new group of antidotes that are effective for OP poisoning treatments is desirable. A number of chemicals have been in-silico screened for their potential as malathion-inhibited acetylcholinesterase (AChE) poisoning antidotes. This screening narrows down the selection of the compounds to be synthesized, therefore reduce the time and cost needed to produce the reactivators. YASARA, a bioinformatics tool was used to perform the docking study of malathion-inhibited human AChE and reactivator-malathion inhibited AChE complexations. Fourteen potential compounds were chosen for the estimation of their binding energies and nucleophilic attack distances with malathion inhibited AChE complexes to determine their antidote capabilities. A commercially available antidote, 2-PAM was used for the comparison. Based on their energies and nucleophilic attack distance with malathion-inhibited human AChE, 4-hydroxybenzohydrazide, could also be used as the antidotes.