Design, synthesis and biological studies of carbazole-thiosemicarbazone hybrids as potential topoisomerase II catalytic inhibitors.

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.