Inhibition of AChE by malathion and some structurally similar compounds

Abstract

Inhibition of bovine erythrocyte acetylcholinesterase (free and immobilized on controlled pore glass) by separate and simultaneous exposure to malathion and malathion transformation products which are generally formed during storage or through natural or photochemical degradation was investigated. Increasing concentrations of malathion, its oxidation product malaoxon, and its isomerisation product isomalathion inhibited free and immobilized AChE in a concentration-dependent manner. K I , the dissociation constant for the initial reversible enzyme inhibitor-complex, and k 3 , the first order rate constant for the conversion of the reversible complex into the irreversibly inhibited enzyme, were determined from the progressive development of inhibition produced by reaction of native AChE with malathion, malaoxon and isomalathion. .2) £ 10 26 M, were obtained from the inhibition curves induced by malathion, malaoxon and isomalathion, respectively. However, the products formed due to photoinduced degradation, phosphorodithioic O,O,S-trimethyl ester and O,O-dimethyl thiophosphate, did not noticeably affect enzymatic activity, while diethyl maleate inhibited AChE activity at concentrations . 10 mM. Inhibition of acetylcholinesterase increased with the time of exposure to malathion and its inhibiting by-products within the interval from 0 to 5 minutes. Through simultaneous exposure of the enzyme to malaoxon and isomalathion, an additive effect was achieved for lower concentrations of the inhibitors (in the presence of malaoxon/isomalathion at concentrations 2 £ 10 27 M/2 £ 10 27 M, 2 £ 10 27 M/3 £ 10 27 M and 2 £ 10 27 M/4.5 £ 10 27 M), while an antagonistic effect was obtained for all higher concentrations of inhibitors. The presence of a non-inhibitory degradation product (phosphorodithioic O,O,S-trimethyl ester) did not affect the inhibition efficiencies of the malathion by-products, malaoxon and isomalathion.

Rapid and label-free screening of enzyme inhibitors using segmented flow electrospray ionization mass spectrometry

“…Neostigmine resulted in two IC 50 values, 50 Ϯ 25 M and 38 Ϯ 10 nM, based on two-site competition fitting. These numbers generally agreed well with previously reported values (eserine 72-109 nM [34], malathion 370 M [35], edrophonium 5.4 M [36], and neostigmine 11.3 nM [37]; however, direct comparison of these numbers might not be appropriate because the experimental conditions were not identical (e.g., use of surrogate substrates and different AchE in other assays).…”

Acetylcholinesterase Inhibitors: Pharmacology and Toxicology

“…OP degradation processes also occur in chemical treatments for purification of polluted waters, generally referred as advanced oxidation processes, as well as throughout the enzymatic reactions in birds, fish, insects and mammals. Degradation studies revealed different kinetics, mechanisms and transformation products, suggesting complete mineralization of the starting compound (usually thio form), but forming toxic break down products as well [89, 97-100]. Actually, oxidation and isomerisation reaction products were reported as much more potent AChE inhibitors compared to the starting thio OPs, while hydrolysis products do not noticeably affect the enzyme activity.…”

Immobilization of rat brain acetylcholinesterase on porous gold-nanoparticle–CaCO3 hybrid material modified Au electrode for detection of organophosphorous insecticides

“…Malathion is a broad-spectrum insecticide and chosen as a model compound, because it has been one of the most commonly applied OPs since 1956 [34]. Hence, in the present work it was chosen as standard pesticide for the AChE inhibition.…”