Cholinesterases and amyloid beta are one of the major biological targets in the search for a new and efficacious treatment of Alzheimer's disease. The study describes synthesis and pharmacological evaluation of new compounds designed as dual binding site acetylcholinesterase inhibitors. Among the synthesized compounds, two deserve special attention--compounds 42 and 13. The former is a sacchari...

OBJECTIVE(S) Alzheimer's disease (AD) is a neurodegenerative disorder in elderly patients. Decrease in cholinergic neurotransmission is the main known cause in the pathophysiology of the disease. Improvement and potentiation of the cholinergic system could be beneficial for treatment of the AD. Acetylcholinesterase inhibitors such as donepezil can enhance the duration of action of acetylcholine...

Daphnia magna is a freshwater microcrustacean which is often used for acute and chronic toxicity testing in aquatic ecotoxicology. Recently, tests with daphnids have been used to prescreen the toxicity of newly synthesized acetylcholinesterase reactivators (oximes), which appear as weak inhibitors of acetylcholinesterase (AChE). In our study we investigated and compared the toxicity of five rev...

In this study neurite outgrowth from cultured hippocampal neurones was increased by addition of acetylcholinesterase acting in a non-cholinergic manner. Only monomeric acetylcholinesterase, a form of acetylcholinesterase dominant in development, increased neurite outgrowth (3-10 U/ml); moreover this effect was not blocked by active site blockers (echothiophate and galanthamine) but was sensitiv...

Galanthamine, physostigmine and 9-amino-1,2,3,4-tetrahydroacridine (tacrine) were evaluated as inhibitors of human acetylcholinesterase activity from samples of postmortem human brain, fresh brain cortex biopsies and human erythrocytes. Acetylcholinesterase activity was most effectively inhibited in all tissues by physostigmine, followed by tacrine and galanthamine. The respective inhibitor con...

Alzheimer's disease (AD) is an age-dependent neurodegenerative disorder and the most common cause of dementia. The early stages of AD are characterized by short-term memory loss. Once the disease progresses, patients experience difficulties in sense of direction, oral communication, calculation, ability to learn, and cognitive thinking. The median duration of the disease is 10 years. The pathol...

The AChE inhibitory activity of alkaloid extracts and compounds has been in the focus research on plants Amaryllidoideae subfamily since approval galanthamine 2001 by FDA for treatment mild to moderate Alzheimer's disease. A small fraction huge biodiversity producing Amaryllidaceae alkaloids studied as a source inhibitors. Less than 20% known have tested vitro their ability inhibit AChE. Galant...