多环咔唑衍生物:通过拓扑异构酶 II 催化抑制和诱导细胞凋亡揭示其抗增殖作用

IF 5.6 2区 医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY
Mateusz Olszewski, Natalia Maciejewska, Anoop Kallingal, Agnieszka Chylewska, Aleksandra M Dąbrowska, Małgorzata Biedulska, Mariusz Makowski, José M Padrón, Maciej Baginski
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引用次数: 0

摘要

人类 DNA 拓扑异构酶对 DNA 复制、转录、染色质凝结及其结构维护等关键细胞过程至关重要。治疗癌症的重要策略之一是抑制一种特定类型的拓扑异构酶,即拓扑异构酶 II(Topo II)。咔唑衍生物具有多种生物活性,最近已成为肿瘤研究的一个重要焦点。本研究评估了三种对称取代的咔唑衍生物:2,7-二(2-呋喃基)-9H-咔唑(27a)、3,6-二(2-呋喃基)-9H-咔唑(36a)和 3,6-二(2-噻吩基)-9H-咔唑(36b)作为抗癌剂的功效。在所研究的咔唑衍生物中,含有两个呋喃分子的 3,6-二(2-呋喃基)-9H-咔唑化合物成为 Topo II 的新型催化抑制剂。值得注意的是,3,6-二(2-呋喃基)-9H-咔唑能有效地选择性抑制 Topo IIα 的松弛和脱atenation 活性,而对 IIβ 异构体的影响极小。这些发现强调了 3,6-二(2-呋喃基)-9H-咔唑化合物作为一种有潜力的候选先导化合物的潜力,值得在抗癌药物开发领域进行进一步研究。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Palindromic carbazole derivatives: unveiling their antiproliferative effect via topoisomerase II catalytic inhibition and apoptosis induction.

Human DNA topoisomerases are essential for crucial cellular processes, including DNA replication, transcription, chromatin condensation, and maintenance of its structure. One of the significant strategies employed in cancer treatment involves the inhibition of a specific type of topoisomerase, known as topoisomerase II (Topo II). Carbazole derivatives, recognised for their varied biological activities, have recently become a significant focus in oncological research. This study assesses the efficacy of three symmetrically substituted carbazole derivatives: 2,7-Di(2-furyl)-9H-carbazole (27a), 3,6-Di(2-furyl)-9H-carbazole (36a), and 3,6-Di(2-thienyl)-9H-carbazole (36b) - as anticancer agents. Among investigated carbazole derivatives, compound 3,6-di(2-furyl)-9H-carbazole bearing two furan moieties emerged as a novel catalytic inhibitor of Topo II. Notably, 3,6-di(2-furyl)-9H-carbazole effectively selectively inhibited the relaxation and decatenation activities of Topo IIα, with minimal effects on the IIβ isoform. These findings underscore the potential of compound 3,6-Di(2-furyl)-9H-carbazole as a promising lead candidate warranting further investigation in the realm of anticancer drug development.

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来源期刊
CiteScore
10.30
自引率
10.70%
发文量
195
审稿时长
4-8 weeks
期刊介绍: Journal of Enzyme Inhibition and Medicinal Chemistry publishes open access research on enzyme inhibitors, inhibitory processes, and agonist/antagonist receptor interactions in the development of medicinal and anti-cancer agents. Journal of Enzyme Inhibition and Medicinal Chemistry aims to provide an international and interdisciplinary platform for the latest findings in enzyme inhibition research. The journal’s focus includes current developments in: Enzymology; Cell biology; Chemical biology; Microbiology; Physiology; Pharmacology leading to drug design; Molecular recognition processes; Distribution and metabolism of biologically active compounds.
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