Design, Synthesis and Biological Studies of Carbazole-Thiosemicarbazones Hybrids as Potential Topoisomerase II Catalytic Inhibitors

Abstract

In this study, carbazole-thiosemicarbazone hybrids were designed, synthesized and investigated for their topoisomerase II (Topo II) inhibition and antiproliferative activity. The 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 assured the promising binding of the investigated members toward Topo II with potential 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, inhibit the migration, and inhibit the clonogenic survival of MG63 cells.