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Synthesis and characterization of novel 1, 2-oxazine-based small molecules that targets acetylcholinesteraseстатья
Информация о цитировании статьи получена из
Web of Science,
Scopus
Статья опубликована в журнале из списка Web of Science и/или Scopus
Дата последнего поиска статьи во внешних источниках: 19 сентября 2017 г.
- Авторы: Sukhorukov Alexey Yu, Nirvanappa Anilkumar C., Jagadish Swamy, Ioffe Sema L., Shivananju Nanjunda Swamy, Rangappa Kanchugarakoppal S.
- Журнал: Bioorganic and Medicinal Chemistry Letters
- Том: 24
- Номер: 15
- Год издания: 2014
- Издательство: Pergamon Press Ltd.
- Местоположение издательства: United Kingdom
- Первая страница: 3618
- Последняя страница: 3621
- DOI: 10.1016/j.bmcl.2014.05.040
- Аннотация: Thirteen 2-oxazine-based small molecules were synthesized targeting 5-lipoxygenase (LOX), and acetylcholinesterase (AChE). The test revealed that the newly synthesized compounds had potent inhibition towards both 5-LOX and AChE in lower micro molar concentration. Among the tested compounds, the most active compound, 2-[(2-acetyl-6,6-dimethyl-4-phenyl-5,6-dihydro-2H-1,2-oxazin-3-yl)methyl]-1H-isoindole-1,3(2H)-dione (2a) showed inhibitory activity towards 5-LOX and AChE with an IC50 values of 1.88, and 2.5 μM, respectively. Further, the in silico molecular docking studies revealed that the compound 2a bound to the catalytic domain of AChE strongly with a highest CDOCKER score of −1.18 kcal/mol when compared to other compounds of the same series. Additionally, 2a showed a good lipophilicity (log P = 2.66), suggesting a potential ability to penetrate the blood–brain-barrier. These initial pharmacological data revealed that the compound 2a could serve as a drug-seed in developing anti-Alzheimer’s agents.
- Добавил в систему: Сухоруков Алексей Юрьевич