1. Novel resveratrol-based flavonol derivatives: Synthesis and anti-inflammatory activity in vitro and in vivo.
- Author
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Chen, Liu Zeng, Yao, Li, Jiao, Ming Ming, Shi, Jing Bo, Tan, Yue, Ruan, Ban Feng, and Liu, Xin Hua
- Subjects
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RESVERATROL , *STRUCTURE-activity relationships , *LUNG injuries , *PROTEIN expression , *ANTI-inflammatory agents , *BIOCHEMICAL mechanism of action - Abstract
In order to discover novel anti-inflammatory agents, total thirty-seven new resveratrol-based flavonol derivatives were designed and synthesized. All compounds have been screened for their anti-inflammatory activity by evaluating their inhibition effect of LPS-induced NO production in RAW 264.7 macrophages. Their toxicity was also assessed in vitro. Structure-activity relationships (SARs) have been concluded, and finally 2-(2,4-dimethoxy-6-(4-methoxystyryl)phenyl)-3-hydroxy-4H-chromen-4-one was found to be the most active scaffold with low toxicity. This compound could significantly decrease productions of NO, IL-6 and TNF-α with IC 50 values of 1.35, 1.12 and 1.92 μM, respectively in RAW 264.7 macrophages. Preliminary mechanism studies indicated that it could inhibit the expression of TLR4 protein, resulting in activation of the NF-ĸB cell signaling pathway. The in vivo anti-inflammatory activity of this compound could reduce pulmonary inflammation by mouse model of LPS-induced acute lung injury (ALI). We believe these findings would further support studies of rational design of more efficient acute lung injury regulatory inhibitors. New resveratrol-based flavonol derivatives with anti-inflammatory were synthesized. Among them, one compound could significantly decreased production of NO, IL-6 and TNF-α LPS-stimulated. Preliminary mechanism indicated that it could inhibit expression of TLR4, resulting in activation cell signaling pathway NF-ĸB and MAPK. The in vivo anti-inflammatory activity was determined by LPS-induced acute lung injury. Image 1 • Novel resveratrol-based flavonol compounds were synthesized. • Compound showed high anti-inflammatory activity against IL-6、NO and TNF-α. • Preliminary mechanisms of anti-inflammatory action were discovered. [ABSTRACT FROM AUTHOR]
- Published
- 2019
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