Discovery of coumarin-derived imino sulfonates as a novel class of potential cardioprotective agents
Discovery of coumarin-derived imino sulfonates as a novel class of potential cardioprotective agents
复制标题
香豆素衍生的亚氨基磺酸盐作为一类新型潜在心脏保护剂的发现
DOI：
10.1016/j.ejmech.2019.111779
复制
发表时间：
2019-12-15
影响因子：
6.7
通讯作者：
Chen, Ya-Jing
中科院分区：
文献类型：
--
作者：
Wei, Bo;Zhou, Jing;Chen, Ya-Jing
活性氧簇（ROS）的爆发有助于并加剧心脏损伤。外源性补充抗氧化剂或上调内源性抗氧化防御基因可能是心血管疾病的潜在治疗方法。合成了16个香豆素衍生的亚氨基磺酸盐化合物，它们通过促进Nrf 2途径降低细胞内ROS水平而直接减轻氧化应激。基于细胞的实验表明，大多数化合物对H2 O2诱导的H9 c2细胞氧化损伤具有显著的保护活性。具有最高活性和低细胞毒性的化合物5 h被证明通过激活Nrf 2及其下游抗氧化蛋白（即，Nrf 2）的表达来显著去除细胞内ROS积累。HO-1和NQO 1），表明其是一种新的有前途的抗氧化剂和Nrf 2激活剂。总体而言，这些发现表明化合物5 h可以用作潜在的心脏保护剂。此外，我们的研究特点是通过在香豆素中的α，β-不饱和羰基实体中引入磺酰基和氮原子来开发新的抗氧化剂和Nrf 2活化剂，而不是向香豆素本身添加新的官能团或活性片段。(C)2019 Elsevier Masson SAS。All rights reserved.
The burst of reactive oxygen species (ROS) contributes to and exacerbates cardiac injury. Exogenous supplementation of antioxidants or upregulation of endogenous antioxidant defense genes should be the potential therapies for cardiovascular disease. Sixteen coumarin-derived imino sulfonates compounds were synthesized with the ability of attenuating oxidative stress directly by reducing intracellular ROS level via promoting Nrf2 pathway. The cell-based assays showed that most of the compounds had significant protective activity against H2O2-induced oxidative injury in H9c2 cells. Compound 5h with the highest activity and low cytotoxicity was demonstrated to remarkably remove the intracellular ROS accumulation by activating expressions of Nrf2 and its downstream antioxidant proteins (ie. HO-1 and NQO1), indicating a novel promising antioxidant and Nrf2 activator. Overall, these findings demonstrated that compound 5h could serve as a potential cardioprotective agent. Moreover, our study features developing new antioxidants and Nrf2 activators by introducing a sulfonyl group and nitrogen atom to the alpha,beta-unsaturated carbonyl entity in coumarin, rather than adding new functional groups or active fragments to coumarin itself. (C) 2019 Elsevier Masson SAS. All rights reserved.