化学
光催化
活动站点
对接(动物)
组合化学
极表面积
细胞毒性
铅化合物
磺胺
药物发现
李宾斯基五定律
酶
体外
生物化学
分子
催化作用
有机化学
基因
护理部
医学
生物信息学
作者
M. Li,Chuanhao Wang,Shuang Ye,Wei Li,Yanming Zhang,Jianyu Yan,Yongchuang Wang,Hang Yang,Yuelin Wu,Yongqiang Zhang,Huojun Zhang,Zhenyuan Miao
标识
DOI:10.1016/j.bmcl.2024.129621
摘要
The progress of organic synthetic method can promote late-stage lead compound modification and novel active compound discovery. Molecular editing technology in the field of organic synthesis, including peripheral and skeletal editing, facilitates rapid access to molecular diversity of a lead compound. Peripheral editing of CH bond activation is gradually used in lead optimization to afford novel active scaffolds and chemical space exploitation. To develop oridonin derivatives with high anti-inflammatory potency, novel oridonin sulfamides had been designed and synthesized by a scaffold hopping strategy based on a visible-light photocatalysis peripheral editing. All novel compounds revealed measurable inhibition of IL-1β and low cytotoxicity in THP-1 cells. The docking study indicated that the best active compound ZM640 was accommodated in the binding site of NLRP3 with two hydrogen bond interaction. These preliminary results confirm that α, β-unsaturated carbonyl of oridonin is not essential for NLRP3 inhibitory effect. This new oridonin scaffold has its potential to be further developed as a promising class of NLRP3 inhibitors.
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