College of Pharmacy, Chung-Ang University, Seoul 06974, Korea.
College of Pharmacy, Chonnam National University, Gwangju 61186, Korea.
BMB Rep. 2018 Jun;51(6):308-313. doi: 10.5483/bmbrep.2018.51.6.064.
Small-molecule inhibitors are widely used to treat a variety of inflammatory diseases. In this study, we found a novel antiinflammatory compound, 1-[(2R,4S)-2-methyl-4-(phenylamino)-1,2,3,4-tetrahydroquinolin-1-yl]prop-2-en-1-one (MPQP). It showed strong anti-inflammatory effects in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages. These effects were exerted through the inhibition of the production of NO and pro-inflammatory cytokines, such as interleukin (IL)-6, IL-1β, and tumor necrosis factor-α (TNF-α). Furthermore, MPQP decreased the expression levels of inducible NO synthase (iNOS) and cyclooxygenase 2 (COX-2). Additionally, it mediated the inhibition of the phosphorylation of p38, c-Jun N-terminal kinase (JNK), the inhibitor of κBα (IκBα), and their upstream kinases, IκB kinase (IKK) α/β, mitogen-activated protein kinase kinase (MKK) 3/6, and MKK4. Furthermore, the expression of IL-1 receptor-associated kinase 1 (IRAK1) that regulates NF-κB, p38, and the JNK signaling pathways, was also increased by MPQP. These results indicate that MPQP regulates the IRAK1-mediated inflammatory signaling pathways by targeting IRAK1 or its upstream factors. [BMB Reports 2018; 51(6): 308-313].
小分子抑制剂被广泛用于治疗各种炎症性疾病。在这项研究中，我们发现了一种新型的抗炎化合物，1-[(2R,4S)-2-甲基-4-(苯氨基)-1,2,3,4-四氢喹啉-1-基]-2-丙烯-1-酮（MPQP）。它在脂多糖（LPS）刺激的 RAW 264.7 巨噬细胞中显示出强大的抗炎作用。这些作用是通过抑制 NO 和促炎细胞因子的产生来发挥的，如白细胞介素（IL）-6、IL-1β 和肿瘤坏死因子-α（TNF-α）。此外，MPQP 降低了诱导型一氧化氮合酶（iNOS）和环氧化酶 2（COX-2）的表达水平。此外，它介导了 p38、c-Jun N 末端激酶（JNK）、κB 抑制物α（IκBα）及其上游激酶，IκB 激酶（IKK）α/β、丝裂原激活蛋白激酶激酶（MKK）3/6 和 MKK4 的磷酸化的抑制。此外，MPQP 还增加了调节 NF-κB、p38 和 JNK 信号通路的白细胞介素 1 受体相关激酶 1（IRAK1）的表达。这些结果表明，MPQP 通过靶向 IRAK1 或其上游因子来调节 IRAK1 介导的炎症信号通路。[BMB 报告 2018；51(6):308-313]。
