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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引用次数: 0

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. 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.

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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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