Design and synthesis of an N-benzyl 5-(4-sulfamoylbenzylidene-2-thioxothiazolidin-4-one scaffold as a novel NLRP3 inflammasome inhibitor

被引：8

作者：

Zuo, Dongxu ^{[1
]}

Do, Nayeon ^{[1
]}

Hwang, Inhwa ^{[2
]}

Ann, Jihyae ^{[1
]}

Yu, Je-Wook ^{[2
]}

Lee, Jeewoo ^{[1
]}

机构：

[1] Seoul Natl Univ, Coll Pharm, Lab Med Chem, Seoul 08826, South Korea

[2] Yonsei Univ, Dept Microbiol & Immunol, BK 21 Project Med Sci, Coll Med, Seoul 03722, South Korea

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2022年 / 65卷

基金：

新加坡国家研究基金会;

关键词：

NLRP3; Inflammasome; Neuroinflammation; Inhibitor;

D O I：

10.1016/j.bmcl.2022.128693

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A series of N-benzyl 5-(4-sulfamoylbenzylidene-2-thioxothiazolidin-4-one analogs, designed as hybrids of CY09 and JC121, were investigated as inhibitors of NLRP3 inflammasome activation. Among them, compounds 34 and 36 were identified as promising NLRP3 inhibitors by measuring the amount of active caspase-1 p20 and IL-1 beta produced by NLRP3 inflammasome activation. Further studies indicated that both compounds inhibited NLRP3 inflammasome assembly by reducing the formation of NLRP3 and ASC oligomer specks and selectively inhibited only NLRP3 inflammasome activation and not other inflammasomes such as NLRC4 and AIM2.

引用

页数：6

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