Fisetin as a Blueprint for Senotherapeutic Agents - Elucidating Geroprotective and Senolytic Properties with Molecular Modeling.

IF 3.9 2区 化学 Q2 CHEMISTRY, MULTIDISCIPLINARY
Maciej Spiegel
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Abstract

Targeting senescent cells and the factors that accelerate this pathological state has recently emerged as a novel field in medicinal chemistry. As attention shifts to synthetic substances, studies on natural agents are often overlooked. In this paper, we present a detailed computational modeling study that encompasses quantum mechanics and molecular dynamics to elucidate the senotherapeutic activity of fisetin, a natural flavonoid. The mitochondrial environment, serving as a proxy for senescence, received special attention. Throughout the study, fisetin's outstanding geroprotective properties-exhibiting significant potential against ⋅OOH, O2-, and ⋅OH radicals, surpassing those of Trolox or ascorbate-were identified. Furthermore, fisetin demonstrated a high capacity to restore oxidatively damaged biomolecules to their pristine forms, thereby renewing the functionality of proteins and amino acids. The senolytic properties were examined in terms of Bcl-2 and Bcl-xL inhibition. The results indicated that fisetin not only binds effectively to these proteins but also, with appropriate modifications, may exhibit specific selectivity toward either target. This study highlights fisetin's remarkable activity in these areas and provides a molecular description of the underlying processes, paving the way for future research.

非瑟酮作为老年治疗药物的蓝图-用分子模型阐明老年保护和衰老特性。
针对衰老细胞和加速这种病理状态的因素是近年来药物化学研究的一个新领域。随着人们的注意力转向合成物质,对天然物质的研究往往被忽视。在本文中,我们提出了一个详细的计算模型研究,包括量子力学和分子动力学来阐明非瑟酮的老年治疗活性。作为衰老代理的线粒体环境受到了特别的关注。在整个研究过程中,非瑟汀具有显著的抗•OOH、O2•-和•OH自由基的保护作用,超过了Trolox或抗坏血酸盐。此外,非瑟酮显示出将氧化损伤的生物分子恢复到原始形态的高能力,从而更新蛋白质和氨基酸的功能。通过对Bcl-2和Bcl-xL的抑制来检测其抗衰老性能。结果表明,非瑟酮不仅可以有效地与这些蛋白结合,而且通过适当的修饰,可以对任何一个靶标表现出特异性的选择性。这项研究强调了非瑟酮在这些领域的显著活性,并提供了潜在过程的分子描述,为未来的研究铺平了道路。
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来源期刊
Chemistry - A European Journal
Chemistry - A European Journal 化学-化学综合
CiteScore
7.90
自引率
4.70%
发文量
1808
审稿时长
1.8 months
期刊介绍: Chemistry—A European Journal is a truly international journal with top quality contributions (2018 ISI Impact Factor: 5.16). It publishes a wide range of outstanding Reviews, Minireviews, Concepts, Full Papers, and Communications from all areas of chemistry and related fields. Based in Europe Chemistry—A European Journal provides an excellent platform for increasing the visibility of European chemistry as well as for featuring the best research from authors from around the world. All manuscripts are peer-reviewed, and electronic processing ensures accurate reproduction of text and data, plus short publication times. The Concepts section provides nonspecialist readers with a useful conceptual guide to unfamiliar areas and experts with new angles on familiar problems. Chemistry—A European Journal is published on behalf of ChemPubSoc Europe, a group of 16 national chemical societies from within Europe, and supported by the Asian Chemical Editorial Societies. The ChemPubSoc Europe family comprises: Angewandte Chemie, Chemistry—A European Journal, European Journal of Organic Chemistry, European Journal of Inorganic Chemistry, ChemPhysChem, ChemBioChem, ChemMedChem, ChemCatChem, ChemSusChem, ChemPlusChem, ChemElectroChem, and ChemistryOpen.
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