Recent progress in topoisomerase inhibitors as anticancer agents: Research and design strategies for Topo I and II inhibitors via structural optimization.

IF 4.7 2区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Bioorganic Chemistry Pub Date : 2025-09-27 DOI:10.1016/j.bioorg.2025.109040

Guanghuan Shen, Shihao Li, Yu Zhu, Zheng Xu, Xuan Liu, Chunyan Lv, Zhihua Xing, Linlin Cui, Wenlan Li

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Abstract

Topoisomerase (Topo) is a crucial class of enzymes that play significant roles in DNA replication, transcription, and repair. Epidemiological research has highlighted the necessity of topoisomerase for the proliferation and genomic stability of tumor cells. Currently, the main topoisomerase inhibitors used in cancer therapy are toxins and catalytic inhibitors that target topoisomerase I (Topo I) and topoisomerase II (Topo II). These inhibitors hinder tumor cell proliferation by disrupting DNA topology regulation. However, prolonged use of these traditional drugs can lead to issues such as drug resistance, cardiotoxicity, and myelosuppression. Thus, there is a pressing need to develop innovative topoisomerase inhibitors with high efficacy and low toxicity. This review systematically summarizes and analyzes the structural and optimization advances of Topo I and II inhibitors over the past five years, with particular attention to catalytic inhibitors and multitarget agents, aiming to provide new perspectives for the development of safer and more effective small-molecule topoisomerase inhibitors for cancer therapy.

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拓扑异构酶抑制剂抗癌研究进展：基于结构优化的拓扑异构酶抑制剂的研究与设计策略。

拓扑异构酶（Topo）是一类在DNA复制、转录和修复中起重要作用的酶。流行病学研究强调了拓扑异构酶对肿瘤细胞增殖和基因组稳定性的重要性。目前，用于癌症治疗的主要拓扑异构酶抑制剂是靶向拓扑异构酶I （Topo I）和拓扑异构酶II （Topo II）的毒素和催化抑制剂。这些抑制剂通过破坏DNA拓扑调节来阻碍肿瘤细胞增殖。然而，长期使用这些传统药物会导致耐药性、心脏毒性和骨髓抑制等问题。因此，迫切需要开发高效、低毒的新型拓扑异构酶抑制剂。本文系统总结和分析了Topo I和Topo II抑制剂近5年来的结构和优化进展，重点介绍了催化抑制剂和多靶点药物，旨在为开发更安全、更有效的小分子拓扑异构酶抑制剂用于癌症治疗提供新的视角。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Bioorganic Chemistry 生物-生化与分子生物学

CiteScore

9.70

自引率

3.90%

发文量

679

审稿时长

31 days

期刊介绍： Bioorganic Chemistry publishes research that addresses biological questions at the molecular level, using organic chemistry and principles of physical organic chemistry. The scope of the journal covers a range of topics at the organic chemistry-biology interface, including: enzyme catalysis, biotransformation and enzyme inhibition; nucleic acids chemistry; medicinal chemistry; natural product chemistry, natural product synthesis and natural product biosynthesis; antimicrobial agents; lipid and peptide chemistry; biophysical chemistry; biological probes; bio-orthogonal chemistry and biomimetic chemistry. For manuscripts dealing with synthetic bioactive compounds, the Journal requires that the molecular target of the compounds described must be known, and must be demonstrated experimentally in the manuscript. For studies involving natural products, if the molecular target is unknown, some data beyond simple cell-based toxicity studies to provide insight into the mechanism of action is required. Studies supported by molecular docking are welcome, but must be supported by experimental data. The Journal does not consider manuscripts that are purely theoretical or computational in nature. The Journal publishes regular articles, short communications and reviews. Reviews are normally invited by Editors or Editorial Board members. Authors of unsolicited reviews should first contact an Editor or Editorial Board member to determine whether the proposed article is within the scope of the Journal.