Scouting around 1,2,3,4-Tetrahydrochromeno[3,2-c]pyridin-10-ones for Single- and Multitarget Ligands Directed towards Relevant Alzheimer's Targets

A number of 1,2,3,4-tetrahydrochromeno[3,2-c]pyridin-10-one derivatives have been synthesized and screened against different targets involved in the onset and progression of Alzheimer's disease (AD), such as acetyl- and butyrylcholinesterase (AChE and BChE), monoamine oxidases A and B (MAO A and B), aggregation of β-amyloid (Aβ) and reactive oxygen species (ROS) production. Derivatives 1 c, 3 b, 4 and 5 a showed multifaceted profiles of promising anti-AD features and returned well-balanced multitargeting inhibitory activities. Moreover, compound 1 f, a potent and selective human MAO B inhibitor (IC50=0.89 μM), proved to be a safe neuroprotectant in a human neuroblastoma cell line (SH-SY5Y) by improving viability impaired by Aβ1–42 and pro-oxidant insult. Furthermore, structure–activity relationships (SARs) and docking models were derived in order to assist further hit-to-lead optimization stage. © 2020 Wiley-VCH GmbH

Авторы
Purgatorio R.1 , Kulikova L.N. 2 , Pisani L.1 , Catto M.1 , De Candia M. , Carrieri A.1 , Cellamare S.1 , De Palma A. , Beloglazkin A.A. 2 , Reza Raesi G. , Voskressensky L.G. 2 , Altomare C.D.1
Журнал
Издательство
John Wiley and Sons Ltd
Номер выпуска
20
Язык
Английский
Страницы
1947-1955
Статус
Опубликовано
Том
15
Год
2020
Организации
  • 1 Department of Pharmacy-Drug Sciences, University of Bari Aldo Moro, Via E. Orabona 4, Bari, 70125, Italy
  • 2 Organic Chemistry Department, Peoples' Friendship University of Russia (RUDN), 6 Miklukho-Maklaya St., Moscow, 117198, Russian Federation
  • 3 Department of Biosciences, Biotechnologies and Biopharmaceutics, University of Bari Aldo Moro, Via E. Orabona 4, Bari, 70125, Italy
Ключевые слова
Alzheimer's disease; inhibitors; medicinal chemistry; multitarget-directed ligands; tetrahydrochromenopyridinone
Дата создания
02.11.2020
Дата изменения
02.11.2020
Постоянная ссылка
https://repository.rudn.ru/ru/records/article/record/64334/