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Интеллектуальная Система Тематического Исследования НАукометрических данных |
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Synthesis and Anti-Inflammatory Activity of 2-Amino-4,5,6,7-tetrahydrobenzo[b]thiophene-Derived NRF2 Activatorsстатья
- Авторы: Kit-Kay Mak, Shiming Zhang, Epemolu Ola, Dinkova-Kostova Albena T., Wells Geoffrey, Gazaryan Irina G., Sakirolla Raghavendra, Mohd Zulkefeli, Pichika Mallikarjuna Rao
- Журнал: ChemistryOpen
- Том: 11
- Номер: 10
- Год издания: 2022
- Номер статьи: e202200181
- DOI: 10.1002/open.202200181
- Аннотация: This is the first study investigating the nuclear factor (erythroid-derived 2)-like 2 (NRF2) activity of compounds containing a new scaffold, tetrahydrobenzo[b]thiophene. Eighteen compounds were synthesised and confirmed their NRF2 activation through NQO1 enzymatic activity and mRNA expression of NQO1 and HO-1 in Hepa-1c1c7 cells. The compounds disrupted the interaction between Kelch-like ECH-associated protein 1 (KEAP1) and NRF2 via interfering with the KEAP1's Kelch domain. The compounds exhibited anti-inflammatory activity in Escherichia coli Lipopolysaccharide (LPSEc )-stimulated RAW 264.7 cells. The anti-inflammatory activity of the compounds was associated with their ability to activate NRF2. The compounds reversed the elevated levels of pro-inflammatory cytokines (IL-1β, IL-6, TNF-α, and IFN-γ) and inflammatory mediators (PGE2, COX-2, and NF-κB). The compounds were metabolically stable in human, rat, and mouse liver microsomes and showed optimum half-life (T1/2 ) and intrinsic clearance (Clint ). The binding mode of the compounds and physicochemical properties were predicted via in silico studies.
- Добавил в систему: Газарян Ирина Георгиевна
Прикрепленные файлы
| № | Имя | Описание | Имя файла | Размер | Добавлен |
|---|---|---|---|---|---|
| 1. | Полный текст | 2022_CHemOpen.pdf | 2,1 МБ | 16 января 2023 [gazaryan] |