黄酮类化合物及其衍生物作为 DNA 拓扑异构酶抑制剂在各种细胞模型中具有抗癌活性:探索新的作用模式。

IF 9.1 2区 医学 Q1 PHARMACOLOGY & PHARMACY Pharmacological research Pub Date : 2024-10-09 DOI:10.1016/j.phrs.2024.107457
Przemysław Sitarek , Anna Merecz-Sadowska , Joanna Sikora , Malwina Dudzic , Natasza Wiertek-Płoszaj , Laurent Picot , Tomasz Śliwiński , Tomasz Kowalczyk
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引用次数: 0

摘要

类黄酮是一类来源于植物的多种次级代谢产物,因其潜在的抗癌特性而备受关注。这篇综述探讨了类黄酮作为 DNA 拓扑异构酶抑制剂的作用,DNA 拓扑异构酶是 DNA 复制、转录和细胞分裂所必需的关键酶。文章全面概述了类黄酮的分类、生物合成及其广泛的天然存在。文章进一步探讨了类黄酮发挥抗癌作用的分子机制,强调了类黄酮与拓扑异构酶的相互作用。综述对体外和体内研究进行了深入分析,强调了各种类黄酮及其衍生物的拓扑异构酶抑制活性。主要研究结果表明,黄酮类化合物可作为催化抑制剂、毒物或 DNA 中间体发挥作用,影响 I 型和 II 型拓扑异构酶。此外,还研究了黄酮类化合物在拓扑异构酶抑制效力方面的结构-活性关系。这篇综述强调了黄酮类化合物作为开发新型拓扑异构酶抑制剂的先导化合物的潜力,这可能对癌症治疗产生重要影响。不过,它也承认需要进一步研究,以充分了解类黄酮与拓扑异构酶在细胞环境中错综复杂的相互作用。
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Flavonoids and their derivatives as DNA topoisomerase inhibitors with anti-cancer activity in various cell models: Exploring a novel mode of action
Flavonoids, a diverse group of plant-derived secondary metabolites, have garnered significant attention for their potential anti-cancer properties. This review explores the role of flavonoids as inhibitors of DNA topoisomerases, key enzymes essential for DNA replication, transcription, and cell division. The article offers a comprehensive overview of flavonoid classification, biosynthesis, and their widespread natural occurrence. It further delves into the molecular mechanisms through which flavonoids exert their anti-cancer effects, emphasizing their interactions with topoisomerases. The review provides a thorough analysis of both in vitro and in vivo studies that highlight the topoisomerase inhibitory activities of various flavonoids and their derivatives. Key findings demonstrate that flavonoids can function as catalytic inhibitors, poisons, or DNA intercalators, affecting both type I and type II topoisomerases. The structure-activity relationships of flavonoids concerning their topoisomerase inhibitory potency are also examined. This review underscores the potential of flavonoids as promising lead compounds for the development of novel topoisomerase inhibitors, which could have important implications for cancer therapy. However, it also acknowledges the need for further research to fully understand the intricate interactions between flavonoids and topoisomerases within the cellular environment.
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来源期刊
Pharmacological research
Pharmacological research 医学-药学
CiteScore
18.70
自引率
3.20%
发文量
491
审稿时长
8 days
期刊介绍: Pharmacological Research publishes cutting-edge articles in biomedical sciences to cover a broad range of topics that move the pharmacological field forward. Pharmacological research publishes articles on molecular, biochemical, translational, and clinical research (including clinical trials); it is proud of its rapid publication of accepted papers that comprises a dedicated, fast acceptance and publication track for high profile articles.
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