Li PengHui, Xie LiJun, Feng ShiYan, Xiang XuDong, Chen ChunXia, Xu LiangXiong
School of Life Science, Huizhou University Huizhou 516007 Guangdong China
RSC Med Chem. 2025 May 9. doi: 10.1039/d5md00234f.
In this study, carbazole-thiosemicarbazone hybrids were designed, synthesized and investigated for their topoisomerase II (Topo II) inhibition and antiproliferative activity. Results showed that compounds C1 and C3 could significantly inhibit the activity of Topo II at 10 μM. Meanwhile, mechanism studies revealed that these hybrids act as non-intercalative Topo II catalytic inhibitors. Additionally, molecular docking revealed the promising binding of the investigated members toward Topo II, with the potential to occupy the ATPase domain. Interestingly, these hybrids exhibited strong antiproliferative activity against HeLa, A549, LNCaP, and MG63 cancer cell lines. Furthermore, compounds C1 and C3 could significantly induce apoptosis and inhibit the migration and clonogenic survival of MG63 cells.
在本研究中，设计、合成了咔唑-硫代半卡巴腙杂化物，并对其拓扑异构酶II（Topo II）抑制活性和抗增殖活性进行了研究。结果表明，化合物C1和C3在10 μM时可显著抑制Topo II的活性。同时，机制研究表明，这些杂化物作为非嵌入型Topo II催化抑制剂发挥作用。此外，分子对接显示所研究的化合物与Topo II具有良好的结合能力，有可能占据ATP酶结构域。有趣的是，这些杂化物对HeLa、A549、LNCaP和MG63癌细胞系表现出较强的抗增殖活性。此外，化合物C1和C3可显著诱导MG63细胞凋亡，并抑制其迁移和克隆存活。
