{"title":"Multifunctional Molecular Hybrids Photoreleasing Nitric Oxide: Advantages, Pitfalls, and Opportunities.","authors":"Cristina Parisi, Francesca Laneri, Aurore Fraix, Salvatore Sortino","doi":"10.1021/acs.jmedchem.4c01038","DOIUrl":null,"url":null,"abstract":"<p><p>The multifaceted role nitric oxide (NO) plays in human physiology and pathophysiology has opened new scenarios in biomedicine by exploiting this free radical as an unconventional therapeutic against important diseases. The difficulties in handling gaseous NO and the strict dependence of the biological effects on its doses and location have made the light-activated NO precursors, namely NO photodonors (NOPDs), very appealing by virtue of their precise spatiotemporal control of NO delivery. The covalent integration of NOPDs and additional functional components within the same molecular skeleton through suitable linkers can lead to an intriguing class of multifunctional photoactivatable molecular hybrids. In this Perspective, we provide an overview of the recent advances in these molecular constructs, emphasizing those merging NO photorelease with targeting, fluorescent reporting, and phototherapeutic functionalities. We will highlight the rational design behind synthesizing these molecular hybrids and critically describe the advantages, drawbacks, and opportunities they offer in biomedical research.</p>","PeriodicalId":46,"journal":{"name":"Journal of Medicinal Chemistry","volume":null,"pages":null},"PeriodicalIF":6.8000,"publicationDate":"2024-10-10","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.4c01038","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/7/15 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"CHEMISTRY, MEDICINAL","Score":null,"Total":0}
引用次数: 0
Abstract
The multifaceted role nitric oxide (NO) plays in human physiology and pathophysiology has opened new scenarios in biomedicine by exploiting this free radical as an unconventional therapeutic against important diseases. The difficulties in handling gaseous NO and the strict dependence of the biological effects on its doses and location have made the light-activated NO precursors, namely NO photodonors (NOPDs), very appealing by virtue of their precise spatiotemporal control of NO delivery. The covalent integration of NOPDs and additional functional components within the same molecular skeleton through suitable linkers can lead to an intriguing class of multifunctional photoactivatable molecular hybrids. In this Perspective, we provide an overview of the recent advances in these molecular constructs, emphasizing those merging NO photorelease with targeting, fluorescent reporting, and phototherapeutic functionalities. We will highlight the rational design behind synthesizing these molecular hybrids and critically describe the advantages, drawbacks, and opportunities they offer in biomedical research.
一氧化氮(NO)在人体生理和病理生理学中发挥着多方面的作用,这为生物医学开辟了新的前景,即利用这种自由基作为治疗重要疾病的非传统疗法。由于气态 NO 难以处理,而且其生物效应严格依赖于其剂量和位置,因此光活化 NO 前体,即 NO 光载体(NOPDs),因其对 NO 释放的精确时空控制而极具吸引力。通过合适的连接体将 NOPDs 和其他功能成分共价整合到同一分子骨架中,可以产生一类有趣的多功能光活化分子混合物。在本视角中,我们将概述这些分子结构的最新进展,重点介绍那些将 NO 光释放与靶向、荧光报告和光治疗功能相结合的分子结构。我们将重点介绍合成这些分子杂交体背后的合理设计,并批判性地描述它们在生物医学研究中的优势、缺点和机遇。
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.