Synthesis and pharmacological validation of fluorescent diarylsulfonylurea analogues as NLRP3 inhibitors and imaging probes
文献类型：期刊论文
| 作者 | Zhao, Jiannan4,5,7,8; Li, Yongling6,7; Ma, Jing7; Liu, Jingting7; Xiao, Ruoxuan7; Wang, Linlin1; Li, Peng2; He, Yinyan3; Qian, Feng7; Zhang, Ao4,5,7,8
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| 刊名 | EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
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| 出版日期 | 2022-07-05 |
| 卷号 | 237页码:13 |
| 关键词 | NLRP3 Inflammasome Inhibitor Fluorescence imaging Sulfonylurea |
| ISSN号 | 0223-5234 |
| DOI | 10.1016/j.ejmech.2022.114338 |
| 通讯作者 | Sun, Zhen-Liang(Zhenliang6@126.com) ; Ding, Chunyong(chunding@sjtu.edu.cn) |
| 英文摘要 | The NOD-like receptor family pyrin domain-containing protein 3 (NLRP3) is a key cytosolic pattern recognition receptor that senses diverse pathogen- and host-originated threat signals. Aberrant activation of NLRP3 inflammasomes is closely associated with the pathogenesis of various complex inflammatory diseases. Nevertheless, the detailed regulation mechanism of NLRP3 inflammasome and its pathogenic roles in the inflammation progression remain to be fully elucidated. Fluorescent imaging with small molecule probe can provide valuable visualization information on the expression, occupancy and bio-distribution of target protein. Herein, we reported a series of diarylsulfonylurea NLRP3 fluorescent inhibitors bearing an amino benzodiazole fluorophore. Compared to the previously reported NLRP3 fluorescent probes, these inhibitors are more structurally concise and membrane permeable due to no additionally appended fluorophore via a linker. Among this series, compound 13a exhibited the most potent cellular NLRP3 inhibitory effect with an IC50 value of 49 nM, and significantly suppressed LPS/ Nigericin-induced secretion of active caspase-1 and mature IL-1b in a dose-dependent manner to block the activation of NLRP3 inflammasome. Meanwhile, this new probe exhibited promising fluorescent properties for specifically detecting and imaging the LPS-induced or constitutively expressed NLRP3 proteins in RAW264.7 cells. Collectively, probe 13a is a potent NLRP3 fluorescent inhibitor with cellular NLRP3 imaging ability, which is useful for NLRP3 inhibitor screening and related mechanism study. (c) 2022 Elsevier Masson SAS. All rights reserved. |
| WOS关键词 | INFLAMMASOME ; TARGET |
| 资助项目 | National Natural Science Foundation of China[21877120] ; National Natural Science Foundation of China[22177068] ; National Natural Science Foundation of China[81872418] ; Science and Technology Commission of Shanghai Municipality[21ZR1429100] ; Science and Technology Commission of Shanghai Municipality[21S11902000] ; Science and Technology Commission of Shanghai Municipality[21142203500] ; Shanghai Jiao Tong University[AF1700037] ; Shanghai Jiao Tong University[WF220217002] ; Shanghai Jiao Tong University[WH101117001] ; Shanghai Jiao Tong University[WF540162618] |
| WOS研究方向 | Pharmacology & Pharmacy |
| 语种 | 英语 |
| WOS记录号 | WOS:000793638500008 |
| 出版者 | ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/301056]  |
| 专题 | 中国科学院上海药物研究所 |
| 通讯作者 | Sun, Zhen-Liang; Ding, Chunyong |
| 作者单位 | 1.Univ Shanghai Sci & Technol, Sch Hlth Sci & Engn, Shanghai 200093, Peoples R China 2.Univ Macau, Inst Chinese Med Sci, State Key Lab Qual Res Chinese Med, Macau 999078, Peoples R China 3.Tongji Univ, Shanghai Matern & Infant Hosp 1, Dept Gynecol Oncol, Sch Med, Shanghai 201204, Peoples R China 4.Univ Chinese Acad Sci, Beijing 100049, Peoples R China 5.Chinese Acad Sci, Shanghai Inst Mat Med SIMM, Shanghai 201203, Peoples R China 6.Southern Med Univ, Affiliated Fengxian Hosp, Sch Pharmaceut Sci, Shanghai 201499, Peoples R China 7.Shanghai Jiao Tong Univ, Pharm X Ctr, Sch Pharmaceut Sci, Shanghai 200240, Peoples R China 8.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai 201210, Peoples R China |
| 推荐引用方式 GB/T 7714 | Zhao, Jiannan,Li, Yongling,Ma, Jing,et al. Synthesis and pharmacological validation of fluorescent diarylsulfonylurea analogues as NLRP3 inhibitors and imaging probes[J]. EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY,2022,237:13. |
| APA | Zhao, Jiannan.,Li, Yongling.,Ma, Jing.,Liu, Jingting.,Xiao, Ruoxuan.,...&Ding, Chunyong.(2022).Synthesis and pharmacological validation of fluorescent diarylsulfonylurea analogues as NLRP3 inhibitors and imaging probes.EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY,237,13. |
| MLA | Zhao, Jiannan,et al."Synthesis and pharmacological validation of fluorescent diarylsulfonylurea analogues as NLRP3 inhibitors and imaging probes".EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY 237(2022):13. |
入库方式： OAI收割
来源：上海药物研究所
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