A novel indazole derivative, compound Cyy-272, attenuates LPS-induced acute lung injury by inhibiting JNK phosphorylation
A novel indazole derivative, compound Cyy-272, attenuates LPS-induced acute lung injury by inhibiting JNK phosphorylation
复制标题
DOI：
10.1016/j.taap.2021.115648
复制
发表时间：
2021-08-14
影响因子：
3.8
通讯作者：
Chen, Gaozhi
中科院分区：
文献类型：
--
作者：
Liu, Qian;Yan, Hao;Chen, Gaozhi
急性肺损伤(ALI)是一种高发病率、高死亡率的弥漫性肺功能障碍疾病。到目前为止，临床上还没有对ALI进行有效的药物治疗。炎症在ALI的发生发展中起关键作用。因此，抗炎治疗可能是治疗ALI的一种潜在策略。吲哚类化合物是药物分子中最重要的杂环之一，具有广泛的生物学性质，如抗癌、抗炎等。在本研究中，我们研究了新合成的吲唑类化合物CyY-272在体内和体外对脂多糖诱导的ALI的生物学作用。结果表明，Cyy-272能抑制LPS刺激的巨噬细胞释放炎性细胞因子，减轻LPS诱导的ALI。进一步的实验表明，Cyy-272通过抑制JNK的磷酸化而显示抗炎活性。总体而言，我们的研究表明，吲唑类化合物Cyy-272在抑制内毒素诱导的JNK激活和炎症信号方面是有效的。
Acute lung injury (ALI) is a diffuse lung dysfunction disease characterized by high prevalence and high mortality. Thus far, no effective pharmacological treatment has been made for ALI in clinics. Inflammation is critical to the development of ALI. Therefore, anti-inflammation may be a potential therapy strategy for ALI. Indazolecontaining derivatives, representing one of the most important heterocycles in drug molecules, are endowed with a broad range of biological properties, such as anti-cancer and anti-inflammation. In the current study, we investigated the biological effects of Cyy-272, a newly synthesized indazole compound, on LPS-induced ALI both in vivo and in vitro. Results show that Cyy-272 can inhibit the release of inflammatory cytokines in LPSstimulated macrophage and alleviate LPS induced ALI. Further experiment revealed that Cyy-272 exhibit anti inflammation activity by inhibiting JNK phosphorylation. Overall, our studies show that an indazole derivative, Cyy-272, is effective in suppressing LPS-induced JNK activation and inflammatory signaling.