Four novel bisquaternary aldoxime cholinesterase reactivators differing in their chemical structure were prepared. Afterwards, their biological activity was evaluated for their ability to reactivate acetylcholinesterase (AChE; EC 3.1.1.7) and butyryl...
We have evaluated in vitro the potency of 23 oximes to reactivate human erythrocyte acetylcholinesterase (AChE) and plasma butyrylcholinesterase (BChE) inhibited by racemic leptophos-oxon (O-[4-bromo-2,5-dichlorophenyl]-O-methyl phenyl-phosphonate),...
Poisoning with organophosphorus compounds used as pesticides or misused as chemical weapons remains a serious threat to human health and life. Their toxic effects result from irreversible blockade of the enzymes acetylcholinesterase and butyrylcholin...
Organophosphorus insecticides (OPs), acting as serine phosphorylating agents in acetylcholinesterase (AChE), are highly effective neurotoxic insecticides. In our previous research, we found that six herbivorous pests and four ladybirds howed signific...
Organophosphorus agents are potent inhibitors of acetylcholinesterase. Inhibition involves successive chemical events. The first is phosphylation of the active site serine to produce a neutral adduct, which is a close structural analog of the acylati...
The newly developed and very promising acetylcholinesterase reactivator (E)-1- (2-hydroxyiminomethylpyridinium)-4-(4-hydroxyiminomethylpyridinium)-but-2-ene dibromide was prepared using two different pathways via a two-step synthesis involving the ap...
Acetylcholinesterase (AChE) reactivators (oximes) are compounds predominantly targeting the active site of the enzyme. Toxic effects of organophosphates nerve agents (OPNAs) are primarily related to their covalent binding to AChE and butyrylcholinest...
We have in vitro tested the ability of common, commercially available, cholinesterase reactivators (pralidoxime, obidoxime, methoxime, trimedoxime and HI-6) to reactivate human acetylcholinesterase (AChE), inhibited by five structurally different org...
In the present work, we performed a complementary quantum mechanical (QM) study to describe the mechanism by which deprotonated pralidoxime (2-PAM) could reactivate human (Homo sapiens sapiens) acetylcholinesterase (HssAChE) inhibited by the nerve ag...
Alzheimer’s disease (AD) is a multifactorial neurodegenerative disorder. Acetylcholinesterase (AChE) inhibitors constitute a pharmacotherapeutic strategy for AD treatment. Resveratrol has anti-inflammatory, neuroprotective, anticarcinogenic, an...
The therapeutical efficacies of eleven oxime-based acetylcholinesterase reactivators were compared in an in vivo (rat model) study of treatment of intoxication caused by tabun. In this group there were some currently available oximes (obidoxime, trim...
Acetylcholinesterase (AChE) is the key enzyme responsible for deactivating the ACh neurotransmitter. Irreversible or prolonged inhibition of AChE, therefore, elevates synaptic ACh leading to serious central and peripheral adverse effects which fall u...
Preparation of 1-(4-hydroxy-iminomethylpyridinium)-3-pyridiniumpropane dibromide is described. This compound represents a new acetylcholinesterase (AChE) reactivator, which has no substituents on the second pyridinium ring as found in other commonly...
Organophosphorus (OP) compounds are used as both chemical weapons and pesticides. However, these agents are very dangerous and toxic to humans, animals, and the environment. Thus, investigations with reactivators have been deeply developed in order t...
Seven new oxime-based acetylcholinesterase reactivators were compared with three currently available ones (obidoxime, trimedoxime, HI-6) for their ability to lessen cholinesterase inhibition in blood and brain of cyclosarin-treated rats. Oximes were...
A family of novel efficient non-oxime compounds exhibited promising reactivation efficacy for VX and sarin inhibited human acetylcholinesterase was discovered. It was found that aromatic groups coupled to Mannich phenols and the introduction of imida...
Organophosphorus compound exposure remains a present threat through agricultural accidents, warfare, or terrorist activity. The primary mechanism of organophosphorus toxicity is through inhibition of the enzyme acetylcholinesterase, with current emer...
The acetylcholinesterase (AChE) reactivators (e.g., obidoxime, asoxime) became an essential part of organophosphorus (OP) poisoning treatment, together with atropine and diazepam. They are referred to as a causal treatment of OP poisoning, because th...
To discover anti-acetylcholinesterase agents for the treatment of Alzheimer’s disease (AD), a series of novel Schiff base-coumarin hybrids was rationally designed, synthesized successfully, and structurally characterized using Fourier transform...
One of the main problems in the treatment of poisoning with organophosphorus (OPs) inhibitors of acetylcholinesterase (AChE) is low ability of existing reactivators of AChE that are used as antidotes to cross the blood-brain barrier (BBB). In this wo...
Assay of acetylcholinesterase (AChE) activity plays an important role in diagnostic, detection of pesticides and nerve agents, in vitro characterization of toxins and drugs including potential treatments for Alzheimer’s disease. These experiments wer...
Chitosan-decorated liposomes were proposed for the first time for the intranasal delivery of acetylcholinesterase (AChE) reactivator pralidoxime chloride (2-PAM) to the brain as a therapy for organophosphorus compounds (OPs) poisoning. Firstly, the c...
Casualties caused by organophosphorus pesticides are a burden for health systems in developing and poor countries. Such compounds are potent acetylcholinesterase irreversible inhibitors, and share the toxic profile with nerve agents. Pyridinium oxime...
Organophosphates (OPs) are esters of substituted phosphates, phosphonates or phosphoramidates that react with acetylcholinesterase (AChE) by initially transferring the organophosphityl group to a serine residue in the enzyme active site, concomitant...
The present article reviews published efforts to study acetylcholinesterase and butyrylcholinesterase structure and function using computer-based modeling and simulation techniques. Structures and models of both enzymes from various organisms, includ...
The influence of ligand binding to human, mouse and Torpedo californica acetylcholinesterase (EC 3.1.1.7; AChE) backbone structures is analyzed in a pairwise fashion by comparison with X-ray structures of unliganded AChEs. Both complexes with reversi...
Conformations of Cα backbones in X-ray structures of most organophosphate (OP)-inhibited human acetylcholinesterases (hAChEs) have been previously shown to be similar to that of the native hAChE. One of the exceptions is the structure of the diethylp...
For the last six decades, researchers have been focused on finding efficient reactivators of organophosphorus compound (OP)-inhibited acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). In this study, we have focused our research on a new o...
The present work aimed to compare the small, neutral and monoaromatic oxime, isatin-3-oxime (isatin-O), to the commercial ones, pralidoxime (2-PAM) and obidoxime, in a search for a new potential reactivator for acetylcholinesterase (AChE) inhibited b...
Nerve agents and oxon forms of organophosphorus pesticides act as strong irreversible inhibitors of two cholinesterases in the human body: acetylcholinesterase (AChE; EC 3.1.1.7) and butyrylcholinesterase (BChE; EC 3.1.1.8), and are therefore highly...
(1) Background: Human exposure to organophosphorus compounds employed as pesticides or as chemical warfare agents induces deleterious effects due to cholinesterase inhibition. One therapeutic approach is the reactivation of inhibited acetylcholineste...
Alzheimer’s disease (AD) signifies a devastating impact on the quality of life of patients and their families. At a biomolecular level, AD is characterized by the deposition of extracellular plaques of β-amyloid (Aβ), affecting langua...
Dandelion, a herb with medicinal and nutritional properties, was studied for the stability and neuroprotective effects of polyphenols from its flowers, roots, and leaves during in vitro simulated digestion. Using UPLC-QTOF-ESI-MS/MS, 84 phenolic meta...
The ability of two newly developed oximes (K305, K307) to protect tabun-poisoned rats from tabun-induced inhibition of brain acetylcholinesterase, acute neurotoxic signs and symptoms and brain damage was compared with that of the oxime K203 and trime...
Due to their inhibition of acetylcholinesterase, organophosphates are among the most toxic of chemicals. Pralidoxime (a.k.a 2-PAM) is the only acetylcholinesterase reactivator approved in the U.S., but 2-PAM only poorly traverses the blood–brai...
Organophosphoate (OP) chemicals are known to inhibit the enzyme acetylcholinesterase (AChE). Studying OP poisoning is difficult because common small animal research models have serum carboxylesterase, which contributes to animals’ resistance to...
Oxidative catabolism of monoamine neurotransmitters by monoamine oxidases (MAOs) produces reactive oxygen species (ROS), which contributes to neuronal cells’ death and also lowers monoamine neurotransmitter levels. In addition, acetylcholineste...
This article describes acetylcholinesterase (AChE), an enzyme involved in parasympathetic neurotransmission, its activity, and how its inhibition can be pharmacologically useful for treating dementia, caused by Alzheimer’s disease, or as a warf...
We aimed to investigate the antioxidant and acetylcholinesterase inhibitory activities of the anthocyanin rich extract of grape skin. Grape skin anthocyanin (GSA) neutralized free radicals in different test systems, such as 2,-2'-azinobis-(3-ethylben...
Okinawa propolis (OP) and its major ingredients were reported to have anti-cancer effects and lifespan-extending effects on Caenorhabditis elegans through inactivation of the oncogenic kinase, p21-activated kinase 1 (PAK1). Herein, five prenylated fl...
Seven pyridoxal dioxime quaternary salts (1–7) were synthesized with the aim of studying their interactions with human acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). The synthesis was achieved by the quaternization of pyridoxal m...
The inhibition of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) by organophosphates (OPs) as nerve agents and pesticides compromises normal cholinergic nerve signal transduction in the peripheral and central nervous systems (CNS) leadi...
Olesoxime, a cholesterol derivative with an oxime group, possesses the ability to cross the blood–brain barrier, and has demonstrated excellent safety and tolerability properties in clinical research. These characteristics indicate it may serve...
Antioxidant dietary intervention is considered a potential strategy in delaying age-related dysfunctions. In this study of 56 days, we assessed the antioxidant effects of walnut kernel (WK) and walnut septum extract (WSE) in a D-galactose (D-gal)-ind...
Many natural-derived compounds, including the essential oils from plants, are investigated to find new potential protective agents in several neurodegenerative disorders such as Alzheimer’s disease (AD). In the present study, we tested the neuroprote...
Background: Aging involves progressive functional decline driven by oxidative stress and mitochondrial dysfunction, and dietary flavonoids are promising aging interventions due to their multi-target regulatory pathways. Methods: This study systematic...
20 December 2018
It has been reported that donepezil and rivastigmine, the acetylcholinesterase (AchE) inhibitors commonly used in the treatment of Alzheimer’s disease (AD), do not only inhibit AChE but also have antioxidant properties. As oxidative stress is i...
Basal forebrain cholinergic dysfunction, most likely linked with tau protein aggregation, is a characteristic feature of Alzheimer’s disease (AD). Recent evidence suggests that tau protein is a putative target for the treatment of dementia, and...
Acetylcholinesterase (AChE) reactivators were developed for the treatment of organophosphate intoxication. Standard care involves the use of anticonvulsants (e.g., diazepam), parasympatolytics (e.g., atropine) and oximes that restore AChE activity. H...
Alzheimer’s disease (AD) is a multifactorial neurodegenerative disorder that involves different pathogenic mechanisms. In this regard, the goal of this study was the design and synthesis of new compounds with multifunctional pharmacological activity...
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