Min Zhao, Neng Ye, Ling Liu, Rui-Jia Zhang, Na Li, Jing Peng, Xiao-Ying Cai, Xue-Qin Jiang, Kai-Yue Su, Xin-Lu Zhang, Qian-Ru Rao, Kong-Jun Liu, De-Xin Deng, Ai-Hua Peng, Ming-Hai Tang, Li-Juan Chen, Wen-Shuang Wu, Hao-Yu Ye
The NLRP3 inflammasome has been recognized as a promising therapeutic target in drug discovery for inflammatory diseases. Our initial research identified a natural sesquiterpene isoalantolactone (IAL) as the active scaffold targeting NLRP3 inflammasome. To improve its activity and metabolic stability, a total of 64 IAL derivatives were designed and synthesized. Among them, compound 49 emerged as the optimal lead, displaying the most potent inhibitory efficacy on nigericin-induced IL-1β release in THP-1 cells, with an IC50 value of 0...
April 30, 2024: Journal of Medicinal Chemistry