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
收藏
页数：6
相关论文
共 50 条
  • [21] A novel cysteine protease inhibitor in Baylisascaris schroederi migratory larvae regulates inflammasome activation through the TLR4–ROS–NLRP3 pathway
    Jingyun Xu
    Xiaobin Gu
    Yue Xie
    Ran He
    Jing Xu
    Lang Xiong
    Xuerong Peng
    Guangyou Yang
    Parasites & Vectors, 15
  • [22] Synthesis, Molecular Docking and Anticancer Activity of Novel (E)-5-((1-phenyl-1H-1,2,3-triazol-4-YL)Methylene)-2-thioxothiazolidin-4-one Analogues
    Venkatakrishna, Manikala
    Rao, Madhusudhan, V
    IRANIAN JOURNAL OF CHEMISTRY & CHEMICAL ENGINEERING-INTERNATIONAL ENGLISH EDITION, 2021, 40 (06): : 1793 - 1799
  • [23] Novel synthesis of 3,4-dihydro-5-bromo[1,4]oxazin-2-one derivatives, new protease inhibitor scaffold
    Bihel, F
    Kraus, JL
    ORGANIC & BIOMOLECULAR CHEMISTRY, 2003, 1 (05) : 793 - 799
  • [24] Discovery of 2-(6-{[(1R,2R)-2-hydroxycyclohexyl] amino}-4,5-dimethylpyridazin-3-yl)-5-(trifluoromethyl)phenol (ASP0965): A potent, orally active and brain-penetrable NLRP3 inflammasome inhibitor with a novel scaffold for the treatment of α-synucleinopathy
    Inagaki, Yusuke
    Kamikubo, Takashi
    Kuriwaki, Ikumi
    Watanabe, Junko
    Yamaki, Susumu
    Iida, Maiko
    Tomita, Kyoko
    Kakefuda, Kenichi
    Kurokawa, Jun
    Kiso, Tetsuo
    Saba, Kengo
    Koike, Takanori
    BIOORGANIC & MEDICINAL CHEMISTRY, 2025, 118
  • [25] Crystal structure of (Z)-5-(3-methylbenzylidene)-2-thioxothiazolidin-4-one, C13H15NO2S3
    Barakat, Assem
    Al-Majid, Abdullah Mohammed
    Mabkhot, Yahia N.
    Ghabbour, Hazem A.
    Fun, Hoong-Kun
    ZEITSCHRIFT FUR KRISTALLOGRAPHIE-NEW CRYSTAL STRUCTURES, 2015, 230 (03): : 257 - 258
  • [26] Synthesis and anticancer properties of 5-(1H-benzoimidazol-2-ylmethylene)-4-oxo-2-thioxothiazolidin-3-ylcarboxilic acids
    Horishny, Volodymyr
    Chaban, Taras
    Matiychuk, Vasyl
    PHARMACIA, 2021, 68 (01) : 195 - 200
  • [27] Crystal Structure, Hirshfeld Surface Analysis and Computational Studies of Thiazolidin-4-one derivative: (Z)-5-(4-Chlorobenzylidene)-3-(2-ethoxyphenyl)-2-thioxothiazolidin-4-one
    Khelloul, Nawel
    Toubal, Khaled
    Benhalima, Nadia
    Rahmani, Rachida
    Chouaih, Abdelkader
    Djafri, Ayada
    Hamzaoui, Fodil
    ACTA CHIMICA SLOVENICA, 2016, 63 (03) : 619 - 626
  • [28] 'Huisgen reaction' of aldonitrones with N-benzyl maleimide leading to synthesis of 2,3-diaryl-5-benzyl-2H-3,3a,4,5,6,6a-hexahydropyrrolo[3, 4-d]isoxazole-4, 6-diones
    Kaur, J
    Singh, B
    Singal, KK
    INDIAN JOURNAL OF CHEMISTRY SECTION B-ORGANIC CHEMISTRY INCLUDING MEDICINAL CHEMISTRY, 2005, 44 (07): : 1476 - 1480
  • [29] Synthesis of (±)-trans-2-[3-methoxy-4-(4 chlorophenylthioethoxy)-5-(N-methyl-N-hydroxyureidyl)methylphenyl]-5-(3,4,5-trimethoxyphenyl)tetrahydrofuran
    Ram, B
    Balram, B
    Ram, SR
    INDIAN JOURNAL OF CHEMISTRY SECTION B-ORGANIC CHEMISTRY INCLUDING MEDICINAL CHEMISTRY, 2003, 42 (09): : 2063 - 2068
  • [30] DESIGN, SYNTHESIS AND ANTICANCER ACTIVITY OF SOME NOVEL 5-(4-METHOXYPHENYL)-2,4-DIHYDRO-3H-PYRAZOL-3-ONE DERIVATIVES
    Fathy, Usama
    Gouhar, Rasha S.
    Awad, Hanem M.
    ACTA POLONIAE PHARMACEUTICA, 2017, 74 (05): : 1427 - 1436
12345