Discovery of 1,3,4-oxadiazole derivatives containing a bisamide moiety as a novel class of potential cardioprotective agents
European Journal of Medicinal Chemistry(2022)
摘要
Myocardial injury is a nonnegligible problem in cardiovascular diseases and cancer therapy. The functional feature of N-containing heterocycles in the cardiovascular field has attracted much attention in recent years. Herein, we discovered a lead compound 12a containing 1,3,4-oxadiazole by extensive screening of anticancer derivatives containing nitrogen-heterocycle, which exhibited potential protective activity against oxidative stress in cardiomyocytes. Follow-up structure-activity relationship (SAR) studies also highlighted the role of substitution sites and bisamide moiety in enhancing the protective activity against oxidative stress. Specifically, compound 12d exhibited low cytotoxicity under high concentration and potent myocardial protection against oxidative stress in H9c2 cells. Preliminary mechanistic studies showed compound 12d could decrease the expression of cardiac hypertrophy and oxidative stress-related proteins/genes and reduce mitochondria-mediated cell apoptosis, thereby enhancing the cell vitality of injured cardiomyocytes. In this study, 1,3,4-oxadiazole may represent a novel pharmacophore that possesses potential myocardial protection and provides more choices for future optimization of cardiovascular drugs, especially for the treatment of onco-cardiology.
更多查看译文
关键词
1,3,4-Oxadiazole,Myocardial injury,Cardioprotective agents,Onco-cardiology
AI 理解论文
溯源树
样例
![](https://originalfileserver.aminer.cn/sys/aminer/pubs/mrt_preview.jpeg)
生成溯源树,研究论文发展脉络
Chat Paper
正在生成论文摘要