Synthesis, molecular docking, and biological activity of 2-vinyl chromones: Toward selective butyrylcholinesterase inhibitors for potential Alzheimer's disease therapeutics

We investigated the biological activity of a series of substituted chromeno[3,2-c]pyridines, including compounds previously synthesized by our group and novel compounds whose syntheses are reported here. Tandem transformation of their tetrahydropyridine ring under the action of activated alkynes yielding 2-vinylsubstituted chromones was used to prepare nitrogen-containing derivatives of a biologically active chromone system. The inhibitory activity of these chromone derivatives against acetylcholinesterase (AChE), butyrylcholinesterase (BChE) and carboxylesterase (CaE) was investigated using the methods of enzyme kinetics and molecular docking. Antioxidant (antiradical) activity of the compounds was assessed in the ABTS assay. The results demonstrated that a subset of the studied chromone derivatives selectively inhibit BChE but do not exhibit antiradical activity. In addition, the results of molecular docking effectively explained the observed features in the efficacy, selectivity, and mechanism of BChE inhibition by the chromone derivatives. © 2018 Elsevier Ltd

Авторы
Makhaeva G.F.1 , Boltneva N.P.1 , Lushchekina S.V.2 , Rudakova E.V.1 , Serebryakova O.G.1 , Kulikova L.N. 3 , Beloglazkin A.A. 3 , Borisov R.S. 3 , Richardson R.J.4, 5
Редакторы
-
Издательство
-
Номер выпуска
16
Язык
Английский
Страницы
4716-4725
Статус
Опубликовано
Подразделение
-
Номер
-
Том
26
Год
2018
Организации
  • 1 Institute of Physiologically Active Compounds Russian Academy of Sciences, Chernogolovka, 142432, Russian Federation
  • 2 Emanuel Institute of Biochemical Physics Russian Academy of Sciences, Moscow, 119334, Russian Federation
  • 3 Organic Chemistry Department, Faculty of Science, RUDN University, 6 Miklukho-Maklaya St., Moscow, 117198, Russian Federation
  • 4 Department of Environmental Health Sciences, University of Michigan, Ann Arbor, MI 48109, United States
  • 5 Department of Neurology, University of Michigan, Ann Arbor, MI 48109, United States
Ключевые слова
2-vinyl-substituted chromones; Alzheimer's disease; Butyrylcholinesterase inhibitors; Chromenopyridine; Esterase profile; Molecular docking; Tandem transformation, Activated alkynes
Дата создания
19.10.2018
Дата изменения
19.10.2018
Постоянная ссылка
https://repository.rudn.ru/ru/records/article/record/6443/