- Aurone Mannich base derivatives as promising multifunctional agents with acetylcholinesterase inhibition, anti-β-amyloid aggragation and neuroprotective properties for the treatment of Alzheimer's disease
-
A series of aurone Mannich base derivatives were designed, synthesized and evaluated as multifunctional agents for the treatment of Alzheimer's disease. In vitro assays demonstrated that most of the derivatives were selective AChE inhibitors with good multifunctional properties. Among them, compound 7d exhibited outstanding inhibitory activity for RatAChE, EeAChE and HuAChE (IC50= 0.00878 ± 0.0002 μM, 0.0212 ± 0.006 μM and 0.0371 ± 0.004 μM, respectively). Moreover, 7d displayed high antioxidant activity and could confer significant neuroprotective effect against H2O2-induced PC-12 cell injury. In addition, 7d also showed biometal chelating abilities, good self- and Cu2+-induced Aβ1-42aggregation inhibitory potency and high BBB permeability. These multifunctional properties highlight 7d as promising candidate for further studies directed to the development of novel drugs against AD.
- Li, Yan,Qiang, Xiaoming,Luo, Li,Yang, Xia,Xiao, Ganyuan,Liu, Qi,Ai, Jiachen,Tan, Zhenghuai,Deng, Yong
-
-
Read Online
- Synthetic method for aurone compounds and anti-inflammatory compounds containing thereof
-
The present invention relates to a synthesis method capable of synthesizing aurone compounds, Rreogoron A (Compound 1a), Gram-flavonoid A (Compound 1b), and derivatives thereof (Compounds 1c to 1o) in a high yield from the disclosed commercially-available products. Also, their anti-inflammatory effects were evaluated in LPS-induced RAW-264.7 macrophages. The aurone compounds do not show cytotoxicity, and weakens or reduces the generation of nitrogen oxide that is induced by LPS at 10 andmu;M, and the IC_50 values of the compounds 1a - 1o are each in the range of 3.39-19.55 andmu;M. Among 15 aurone compounds synthesized in the present invention, the highest inhibitory activities were shown by the following compounds in this order: the compound 1g (63.98%; IC_50= 4.50), the compound 1o (49.07%; IC_50= 4.98) and the Rreogoron A (41.72%; IC_50= 3.39). Among the aurone compounds derived from 5,6-dimethoxybenzofuran-3(2H)-one (Compound 5), the compounds bound to 4-bromophenyl group (Compound 1g), ferrocenyl group (Compound 1o), and 4-hydroxyphenyl group (Compound 1a) were more effective to iNOS-mediated nitrogen oxide inhibitors than other aurone compounds.COPYRIGHT KIPO 2017
- -
-
-
- Facile synthesis and nitric oxide inhibitory activity of aurones, rugaurone a, gramflavonoid a and their derivatives
-
Facile synthesis of natural aurones, rugaurone A (1a), gramflavonoid A (1b) and their novel derivatives (1c-1o) is accomplished in good to high yields with exceptional Z-selectivity (≥ 97%) from the commercially available starting materials. Herein, practically improved method was developed for the synthesis of common key intermediate, 5,6-dimethoxybenzofuran-3(2H)-one (5). Later, their nitric oxide (NO) production inhibition effects were estimated in lipopolysaccharide (LPS)-induced RAW-264.7 macrophages as an indicator of anti-inflammatory activity. All compounds exhibited weak to good strength against NO production in a concentration-dependent manner and none of the compound showed significant cytotoxicity against macrophages at the highest (10 μM) concentration. The IC50 values are showed in the range from 3.39 to 19.55 μM. Among the 15 aurones synthesized in this study, 3 compounds that is compound 1g (63.98%) followed by compound 1o (49.07%) and rugaurone A (1a) (41.72%) showed the maximum inhibitory activity with respective IC50 values of 4.50 μM, 4.98 μM and 3.39 μM compared to L-NMMA (IC50 = 5.19 μM), which was used as a standard NO inhibitor. This study suggests that compounds 1g, 1o and 1a may serve as favorable structures for further development of NO production-targeted anti-inflammatory agents.
- Damodar, Kongara,Kim, Jin-Kyung,Jun, Jong-Gab
-
p. 1091 - 1098
(2016/11/25)
-