Department of Chemistry, Vanderbilt University, Nashville, TN 37240, USA.
Department of Biological, Physical and Human Sciences, Freed Hardeman University, Henderson, TN 38340, USA.
Int J Mol Sci. 2023 Jul 27;24(15):12010. doi: 10.3390/ijms241512010.
Topoisomerases, common targets for anti-cancer therapeutics, are crucial enzymes for DNA replication, transcription, and many other aspects of DNA metabolism. The potential anti-cancer effects of thiosemicarbazones (TSC) and metal-TSC complexes have been demonstrated to target several biological processes, including DNA metabolism. Human topoisomerases were discovered among the molecular targets for TSCs, and metal-chelated TSCs specifically displayed significant inhibition of topoisomerase II. The processes by which metal-TSCs or TSCs inhibit topoisomerases are still being studied. In this brief review, we summarize the TSCs and metal-TSCs that inhibit various types of human topoisomerases, and we note some of the key unanswered questions regarding this interesting class of diverse compounds.
拓扑异构酶是抗癌治疗的常见靶点，是 DNA 复制、转录和许多其他 DNA 代谢方面的关键酶。硫代氨基甲酸盐（TSC）和金属-TSC 配合物的潜在抗癌作用已被证明针对包括 DNA 代谢在内的多种生物过程。TSC 的分子靶点中发现了人类拓扑异构酶，金属螯合的 TSC 特别显示出对拓扑异构酶 II 的显著抑制作用。金属-TSC 或 TSC 抑制拓扑异构酶的过程仍在研究中。在这篇简短的综述中，我们总结了抑制各种类型的人类拓扑异构酶的 TSC 和金属-TSC，并指出了有关这一有趣的多样化化合物类别的一些关键未解决的问题。
