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新型拓扑异构酶 II 抑制剂的综述:未来的抗癌药物。

A Mini Review of Novel Topoisomerase II Inhibitors as Future Anticancer Agents.

机构信息

Department of Chemistry, Tennessee State University, Boswell Science Complex, Nashville, TN 37209-1561, USA.

出版信息

Int J Mol Sci. 2023 Jan 28;24(3):2532. doi: 10.3390/ijms24032532.

Abstract

Several reviews of inhibitors of topoisomerase II have been published, covering research before 2018. Therefore, this review is focused primarily on more recent publications with relevant points from the earlier literature. Topoisomerase II is an established target for anticancer drugs, which are further subdivided into poisons and catalytic inhibitors. While most of the topoisomerase II-based drugs in clinical use are mostly topoisomerase II poisons, their mechanism of action has posed severe concern due to DNA damaging potential, including the development of multi-drug resistance. As a result, we are beginning to see a gradual paradigm shift towards non-DNA damaging agents, such as the lesser studied topoisomerase II catalytic inhibitors. In addition, this review describes some novel selective catalytic topoisomerase II inhibitors. The ultimate goal is to bring researchers up to speed by curating and delineating new scaffolds as the leads for the optimization and development of new potent, safe, and selective agents for the treatment of cancer.

摘要

已经有几篇关于拓扑异构酶 II 抑制剂的综述发表,涵盖了 2018 年以前的研究。因此,这篇综述主要集中在最近的出版物上,并涉及早期文献中的相关要点。拓扑异构酶 II 是抗癌药物的既定靶点,这些药物进一步分为毒物和催化抑制剂。虽然临床应用中大多数基于拓扑异构酶 II 的药物主要是拓扑异构酶 II 毒物,但由于其潜在的 DNA 损伤,包括多药耐药性的发展,其作用机制引起了严重关注。因此,我们开始看到向非 DNA 损伤剂的逐渐范式转变,例如研究较少的拓扑异构酶 II 催化抑制剂。此外,本综述还描述了一些新型选择性催化拓扑异构酶 II 抑制剂。最终目标是通过整理和描绘新的骨架作为优化和开发新的有效、安全和选择性抗癌药物的先导,使研究人员跟上最新进展。

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