New alicyclic thiosemicarbazone chelated zinc(II) antitumor complexes: Interactions with DNA/protein, nuclease activity and inhibition of topoisomerase-I

Two new zinc(II) complexes, Zn(chtsc-N-Me)2 and Zn(chtsc-N-Ph)2 where chtsc = cyclohexanone thiosemicarbazone; chtsc-N-Ph = cyclohexanone N(4)-phenyl thiosemicarbazone, were isolated and characterized by X-ray crystallography. The interaction of these complexes with DNA and protein were studied using calf thymus DNA (CT-DNA) and bovine serum albumin (BSA) as the respective models, and marked activity was observed. The complexes exhibited efficient DNA cleavage activity via the oxidative pathway involving singlet oxygen as the reactive oxygen species. The topoisomerase inhibition assay showed that, even at low concentrations, both Zn(chtsc-N-Me)2 and Zn(chtsc-N-Ph)2 are capable of impairing enzymatic occupation of human topoisomerase-I, a significant feature of anticancer drugs. The results of in-vitro anti-proliferation tests carried out against five different human tumor cells lines gave GI50 values lower than 5 μg/mL, which indicates that these complexes are potentially advantageous as anticancer agents.

DNA/protein-philic zinc complexes found to cleavage DNA, inhibit topoisomerase activity and suppress cancer cells growth.Figure optionsDownload as PowerPoint slide