{"title":"Design, synthesis and biological studies of carbazole-thiosemicarbazone hybrids as potential topoisomerase II catalytic inhibitors.","authors":"PengHui Li, LiJun Xie, ShiYan Feng, XuDong Xiang, ChunXia Chen, LiangXiong Xu","doi":"10.1039/d5md00234f","DOIUrl":null,"url":null,"abstract":"<p><p>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.</p>","PeriodicalId":21462,"journal":{"name":"RSC medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":4.1000,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12109611/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"RSC medicinal chemistry","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1039/d5md00234f","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
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.
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号
