{"title":"Hypoxia Activated Nitric Oxide Donor Compounds for the Prevention and Treatment of Myocardial Hypoxia-Induced Injury","authors":"Wanxiang Yang, Wen Zhou, Shaohua Gou","doi":"10.1021/acs.jmedchem.4c02132","DOIUrl":null,"url":null,"abstract":"A series of hypoxia-targeted nitric oxide donor compounds were designed and synthesized by using an ether linker to connect <i>N</i>-methyl-<i>N</i>-nitroso-<i>p</i>-phenol and nitrobenzyl alcohols, respectively. Among them, <b>N6</b>, with acceptable pharmacokinetic parameters in mice, exhibited a high selective NO release in H9c2 cells under hypoxia and in the dissected heart tissue of the tested mice as desired. Mechanistic investigations revealed that <b>N6</b> could regulate vascular dilation and modulate proteins associated with myocardial injury both <i>in vitro</i> and <i>in vivo</i>. Animal tests demonstrated that <b>N6</b> showed better therapeutic and preventive effects against myocardial hypoxia injury than the commercial drug isosorbide mononitrate. Our research evidence that <b>N6</b> has a potent therapeutic potential in treating myocardial hypoxic injury, which can be further investigated as a promising drug candidate for coronary heart disease.","PeriodicalId":46,"journal":{"name":"Journal of Medicinal Chemistry","volume":"12 1","pages":""},"PeriodicalIF":6.8000,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Medicinal Chemistry","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1021/acs.jmedchem.4c02132","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CHEMISTRY, MEDICINAL","Score":null,"Total":0}
引用次数: 0
Abstract
A series of hypoxia-targeted nitric oxide donor compounds were designed and synthesized by using an ether linker to connect N-methyl-N-nitroso-p-phenol and nitrobenzyl alcohols, respectively. Among them, N6, with acceptable pharmacokinetic parameters in mice, exhibited a high selective NO release in H9c2 cells under hypoxia and in the dissected heart tissue of the tested mice as desired. Mechanistic investigations revealed that N6 could regulate vascular dilation and modulate proteins associated with myocardial injury both in vitro and in vivo. Animal tests demonstrated that N6 showed better therapeutic and preventive effects against myocardial hypoxia injury than the commercial drug isosorbide mononitrate. Our research evidence that N6 has a potent therapeutic potential in treating myocardial hypoxic injury, which can be further investigated as a promising drug candidate for coronary heart disease.
期刊介绍：
The Journal of Medicinal Chemistry is a prestigious biweekly peer-reviewed publication that focuses on the multifaceted field of medicinal chemistry. Since its inception in 1959 as the Journal of Medicinal and Pharmaceutical Chemistry, it has evolved to become a cornerstone in the dissemination of research findings related to the design, synthesis, and development of therapeutic agents.
The Journal of Medicinal Chemistry is recognized for its significant impact in the scientific community, as evidenced by its 2022 impact factor of 7.3. This metric reflects the journal's influence and the importance of its content in shaping the future of drug discovery and development. The journal serves as a vital resource for chemists, pharmacologists, and other researchers interested in the molecular mechanisms of drug action and the optimization of therapeutic compounds.
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