A series of 2-(4-phenylpiperazin-1-yl)pyrimidine-5-carboxamide derivatives as acetylcholinesterase inhibitors (AChEIs) were designed and synthesized for the treatment Alzheimer’s disease (AD). Their bioactivities evaluated by Ellman’s method, results showed that most compounds displayed moderate inhibitory activities in vitro. Among them, compound 6g exhibited potent activity against AChE with ...

Pyrazolines 7-10 were designed as novel CB(1) receptor antagonists, which exhibited improved turbidimetric aqueous solubilities. On the basis of their extended CB(1) antagonist pharmacophore, hybrid molecules exhibiting cannabinoid CB(1) receptor antagonistic as well as acetylcholinesterase (AChE) inhibiting activities were designed. The target compounds 12, 13, 20, and 21 are based on 1 (tacri...

BACKGROUND Fasciculin (FAS), a 61-residue polypeptide purified from mamba venom, is a three-fingered toxin which is a powerful reversible inhibitor of acetylcholinesterase (AChE). Solution of the three-dimensional structure of the AChE/FAS complex would provide the first structure of a three-fingered toxin complexed with its target. RESULTS The structure of a complex between Torpedo californi...

Chlorpyrifos (CP), an acetylcholinesterase (AChE) inhibitor, is used throughout the world as an insecticide in agriculture and an eradicating agent for termites around homes. In this present study, CP is considered as an oxidative agent which we examine the protective role of zinc oxide nanoparticles (ZnO NPs) in CP-treated lymphocytes of human. Lymphocytes isolated by Ficoll and exposed to 75 ...

The inhibition properties and target sites of monoclonal antibodies (mAbs) Elec403, Elec408 and Elec410, generated against Electrophorus electricus acetylcholinesterase (AChE), have been defined previously using biochemical and mutagenesis approaches. Elec403 and Elec410, which bind competitively with each other and with the peptidic toxin inhibitor fasciculin, are directed toward distinctive a...

We have isolated highly purified coated vesicles from 17-d-old chick embryo skeletal muscle. These isolated coated vesicles contain acetylcholinesterase (AChE) in a latent, membrane-protected form as demonstrated enzymatically and morphologically using the Karnovsky and Roots histochemical procedure (J. Histochem. Cytochem., 1964, 12:219-221). By the use of appropriate inhibitors the cholineste...

Two esters, N-["Clmethylpiperidyl acetate ([WIAMP) and N-["C]methylpiperidyl propionate PCIPMP), were synthesized in no-carrier-added forms and evaluated as in vivo substrates for brain acetylcholinesterase (AChE). After peripheral injection in mice, each ester showed rapid penetration into the brain and a regional retention of radioactivity (striatum > cortex, hippocampus > cerebellum) reflect...

A series of 1,2,3,4-tetrahydrobenzo[h][1,6]naphthyridines differently substituted at positions 1, 5, and 9 have been designed from the pyrano[3,2-c]quinoline derivative 1, a weak inhibitor of acetylcholinesterase (AChE) with predicted ability to bind to the AChE peripheral anionic site (PAS), at the entrance of the catalytic gorge. Fourteen novel benzonaphthyridines have been synthesized throug...

Acetylcholinesterase (AChE) is an essential enzyme that terminates cholinergic transmission by a rapid hydrolysis of the neurotransmitter acetylcholine. AChE is an important target for treatment of various cholinergic deficiencies, including Alzheimer's disease and myasthenia gravis. In a previous high throughput screening campaign, we identified the dye crystal violet (CV) as an inhibitor of A...

The aim of this work was to evaluate, in vitro, the effect of L-alanine (Ala) on suckling rat brain acetylcholinesterase (AChE) and on eel Electrophorus electricus pure AChE inhibited by L-phenylalanine (Phe) as well as to investigate whether Phe or Ala is a competitive inhibitor or an effector of the enzyme. AChE activity was determined in brain homogenates and in the pure enzyme after 1 h pre...