新型4/5取代3-芳基烯-2-氧吲哚衍生物的合成及其作为NQO2配体和NLRP3下调因子的生物学评价

IF 2.2 4区医学 Q3 CHEMISTRY, MEDICINAL

Bioorganic & Medicinal Chemistry Letters Pub Date : 2025-08-14 DOI:10.1016/j.bmcl.2025.130372

Elena N. Bezsonova , Meriam Dubar , Daria D. Melekhina , Mariia A. Salykina , Ivan V. Boichenko , Denis A. Babkov , Roman D. Danilov , Alexander A. Spasov , Natalia A. Lozinskaya

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引用次数: 0

摘要

醌氧化还原酶II （NQO2）是一种与活性氧产生有关的黄蛋白，使其成为抗炎药物的潜在靶点。之前，我们证明了2-氧吲哚衍生物是NQO2的有效抑制剂。本文合成了新型的4/5-取代3-芳基烯-2-氧吲哚，并对其在体外对NQO2的亲和力进行了评价。所得化合物对NQO2的活化率高达85% %。一些衍生的NQO2激活剂在LPS + atp刺激的小鼠巨噬细胞中通过NLRP3炎性体激活显示出抗炎活性。所得化合物经乳酸脱氢酶测定显示为无毒。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

Synthesis of novel 4/5-substituted 3-arylidene-2-oxindole derivatives and their biological evaluation as NQO2 ligands and NLRP3 downregulators

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Synthesis of novel 4/5-substituted 3-arylidene-2-oxindole derivatives and their biological evaluation as NQO2 ligands and NLRP3 downregulators

Quinone oxidoreductase II (NQO2) is a flavoprotein implicated in reactive oxygen species production which can be considered a potential target for anti-inflammatory drugs. Previously, we demonstrated that 2-oxindole derivatives are effective inhibitors of NQO2. In this work, novel 4/5-substituted 3-arylidene-2-oxindoles were synthesized and their affinity towards NQO2 was assessed in vitro. The obtained compounds activated NQO2 up to 85 %. Some derived NQO2 activators showed anti-inflammatory activity via NLRP3 inflammasome activation in LPS + ATP-stimulated murine macrophages. The obtained compounds were shown to be non-toxic in LDH-assay.

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来源期刊

Bioorganic & Medicinal Chemistry Letters 医学-医药化学

CiteScore

5.70

自引率

3.70%

发文量

463

审稿时长

27 days

期刊介绍： Bioorganic & Medicinal Chemistry Letters presents preliminary experimental or theoretical research results of outstanding significance and timeliness on all aspects of science at the interface of chemistry and biology and on major advances in drug design and development. The journal publishes articles in the form of communications reporting experimental or theoretical results of special interest, and strives to provide maximum dissemination to a large, international audience.