Synthesis, in vitro and docking studies of 2-substituted 5,6,7,8-tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidine-4(3H)-one derivatives as agents for the treatment of Alzheimer's disease

Abstract

Alzheimer's disease is a chronic neurodegenerative disease, which is characterized mainly by a progressive decrease in intellectual abilities, memory impairment and a change in a person's personality. Unfortunately, there are practically no medicines that act on pathogenesis of Alzheimer's disease. The development of new highly effective medicines for the treatment of this pathology is an actual area of pharmaceutical research. The aim of this work is to search among 2-substituted 5,6,7,8-tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidine-4(3H)-one effective compounds with an anticholinesterase and an antiamyloid activities. As a result, it was found that compounds 4d, 4e and 4f have the high anticholinesterase ability, which in their structure contain residues of hydroxy-methoxyphenyl fragments. Structures 4c, 4g, 4h, 4j, 4k, 4m, 4n and 4p showed slightly less activity, the effect of which did not differ statistically from that of Donepezil. Compounds 4c, 4e, 4k and 4m have the greatest ability to inhibit the formation of the amyloid, comparable to GV-971. It should be noted that the molecular docking data are consistent with the results of the determination of the anticholinesterase activity of the studied compounds obtained in vitro. Thus, the prospects for future studies of these compounds in the possibility of creating a pharmaceutical active substance for the treatment of neurodegenerative diseases have been revealed.

Chemical Composition And Biological Activity Of Secondary Metabolites From Cuscuta Campestris

“…Помимо этого, данные извлечения ингибировали активность ацетилхолинэстеразы центральной нервной системы на уровне малонового диальдегида. Антихолинэстеразные средства применяют для коррекции холинергической недостаточности при нейродегенеративной патологии, включая болезнь Альцгеймера [74][75][76]. Также экстракты снижали уровни интерлейкина-1β и фактора некроза опухоли-α в головном мозге.…”

In silico и in vitro изучение антитирозиназной активности новых оснований Шиффа — азометиновых производных 2-Амино-4,5,6,7-тетрагидро-1-бензотиофен-3-карбоксамида

“…Согласно данным фармакологического скрининга in vitro, они обладают антихолинэстеразной и антиамилоидной активностью, что обуслав-ливает их гипотетическое применение для лечения болезни Альцгеймера. Структуры синтезированных соединений были подтверждены данными ИК-спектроскопии, 1 H и 13 C ЯМР [11][12][13].…”