Discovery Of Novel Pterostilbene-Based Derivatives As Potent And Orally Active Nlrp3 Inflammasome Inhibitors With Inflammatory Activity For Colitis
JOURNAL OF MEDICINAL CHEMISTRY(2021)
Abstract
Studies have shown that the abnormal activation of the NLRP3 inflammasome is involved in a variety of inflammatory-based diseases. In this study, a high content screening model targeting the activation of inflammasome was first established and pterostilbene was discovered as the active scaffold. Based on this finding, total of 50 pterostilbene derivatives were then designed and synthesized. Among them, compound 47 was found to be the best one for inhibiting cell pyroptosis [inhibitory rate (IR) = 73.09% at 10 mu M], showing low toxicity and high efficiency [against interleukin-1 beta (IL-1 beta): half-maximal inhibitory concentration (IC50) = 0.56 mu M]. Further studies showed that compound 47 affected the assembly of the NLRP3 inflammasomes by targeting NLRP3. The in vivo biological activity showed that this compound significantly alleviated dextran sodium sulfate (DSS)-induced colitis in mice. In general, our study provided a novel lead compound directly targeting the NLRP3 protein, which is worthy of further research and structural optimization.
MoreTranslated text
Key words
active nlrp3 inflammasome inhibitors,inflammatory activity,pterostilbene-based
AI Read Science
Must-Reading Tree
Example
![](https://originalfileserver.aminer.cn/sys/aminer/pubs/mrt_preview.jpeg)
Generate MRT to find the research sequence of this paper
Chat Paper
Summary is being generated by the instructions you defined