On September 1, 2019, Zueva, Irina; Dias, Jose; Lushchekina, Sofya; Semenov, Vyacheslav; Mukhamedyarov, Marat; Pashirova, Tatiana; Babaev, Vasiliy; Nachon, Florian; Petrova, Natalia; Nurullin, Leniz; Zakharova, Lucia; Ilyin, Victor; Masson, Patrick; Petrov, Konstantin published an article.Quality Control of 6-Methylpyrimidine-2,4(1H,3H)-dione The title of the article was New evidence for dual binding site inhibitors of acetylcholinesterase as improved drugs for treatment of Alzheimer’s disease. And the article contained the following:
Profound synaptic dysfunction contributes to early loss of short-term memory in Alzheimer’s disease. This study was set up to analyze possible neuroprotective effects of two dual binding site inhibitors of acetylcholinesterase (AChE), a new 6-methyluracil derivative, C-35, and the clin. used inhibitor donepezil. Crystal structure of the complex between human AChE and C-35 revealed tight contacts of ligand along the enzyme active site gorge. Mol. dynamics simulations indicated that the external flexible part of the ligand establishes multiple transient interactions with the enzyme peripheral anionic site. Thus, C-35 is a dual binding site inhibitor of AChE. In transgenic mice, expressing a chimeric mouse/human amyloid precursor protein and a human presenilin-1 mutant, C-35 (5 mg/kg, i.p) and donepezil (0.75 mg/kg, i.p) partially reversed synapse loss, decreased the number of amyloid plaques, and restored learning and memory. To sep. temporal symptomatic therapeutic effects, associated with the increased lifetime of acetylcholine in the brain, from possible disease-modifying effect, an exptl. protocol based on drug withdrawal from therapy was performed. When administration of C-35 and donepezil was terminated three weeks after the trial started, animals that were receiving C-35 showed a much better ability to learn than those who received vehicle or donepezil. Our results provide addnl. evidence that dual binding site inhibitors of AChE have Alzheimer’s disease-modifying action. The experimental process involved the reaction of 6-Methylpyrimidine-2,4(1H,3H)-dione(cas: 626-48-2).Quality Control of 6-Methylpyrimidine-2,4(1H,3H)-dione
The Article related to alzheimers disease acetylcholinesterase c35 donepezil, alzheimer’s disease, inhibitors of cholinesterase, methyluracil derivatives, β-amyloid, Pharmacology: Effects Of Nervous System- and Behavior-Affecting Drugs and Neuromuscular Agents and other aspects.Quality Control of 6-Methylpyrimidine-2,4(1H,3H)-dione
Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia