Identification of benzofused five-membered sultams, potent dual NOD1/NOD2 antagonists in vitro and in vivo
Identification of benzofused five-membered sultams, potent dual NOD1/NOD2 antagonists in vitro and in vivo
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苯并稠合五元磺内酯、强效双重 NOD1/NOD2 拮抗剂的体外和体内鉴定
DOI：
10.1016/j.ejmech.2020.112575
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发表时间：
2020-10-15
影响因子：
6.7
通讯作者：
Liu, Gang
中科院分区：
文献类型：
--
作者：
Ma, Yao;Li, Xueyuan;Liu, Gang
含核苷酸结合寡聚化结构域的蛋白1和2在免疫系统激活中起重要作用。最近，由于新出现的知识，即阻止核苷酸结合寡聚化结构域（NOD）信号传导可以促进某些癌症的治疗，这使得寻找NOD 1和NOD 2的双重拮抗剂成为可能，因此发生了转变。在此，我们进行了一类新的衍生物的双重NOD 1/NOD 2拮抗剂与新的苯并稠合的五元磺内酰胺的合成和鉴定。最终证明化合物14 k是在体外和体内抑制NOD 1和NOD 2刺激的NF-κ B和MAPK信号传导的最有效的分子。(C)2020 Elsevier Masson SAS。All rights reserved.
Nucleotide-binding oligomerization domain-containing proteins 1 and 2 play important roles in immune system activation. Recently, a shift has occurred due to the emerging knowledge that preventing nucleotide-binding oligomerization domains (NODs) signaling could facilitate the treatment of some cancers, which warrants the search for dual antagonists of NOD1 and NOD2. Herein, we undertook the synthesis and identification of a new class of derivatives of dual NOD1/NOD2 antagonists with novel benzofused five-membered sultams. Compound 14k was finally demonstrated to be the most potent molecule that inhibits both NOD1-and NOD2-stimulated NF-kappa B and MAPK signaling in vitro and in vivo. (C) 2020 Elsevier Masson SAS. All rights reserved.