Dinuclear zinc bis(thiosemicarbazone) complexes: Synthesis, in vitro anticancer activity, cellular uptake and DNA interaction study

•New dinuclear zinc bis(thiosemicarbazone) complexes are reported.•Cytotoxicity depends on the terminal substituent and the length of the linker.•The cellular uptake and fluorescence properties have been investigated.•Complexes bind to DNA via electrostatic mode without causing significant cleavage.

Four dinucleating bis(thiosemicarbazone) ligands and their zinc complexes have been synthesized and characterized by multinuclear NMR (1H and 13C), IR, UV–Vis, ESI-MS and fluorescence spectroscopic techniques. Their purity was assessed by elemental analysis. Cytotoxicity was tested against five human cancer cell lines using the sulphorhodamine B (SRB) assay, where one of the complexes, 1,3-bis{biacetyl-2′-(4″-N-pyrrolidinylthiosemicarbazone)-3′-(4″-N-pyrrolidinylthiosemicarbazone)zinc(II)}propane (6), was found to be quite cytotoxic against MCF-7 (breast cancer) and HepG2 (hepatoma cancer) cell lines, with a potency similar to that of the well known anticancer drug adriamycin. It is evident from the cellular uptake studies that the uptake is same for the active complex 6 and the inactive complex 8 (1,6-bis{biacetyl-2′-(4″-N-pyrrolidinylthiosemicarbazone)-3′-(4″-N-pyrrolidinylthiosemicarbazone)zinc(II)}hexane) in MCF-7 and HepG2 cell lines. In vitro DNA binding and cleavage studies revealed that all complexes bind with DNA through electrostatic interaction, and cause no significant cleavage of DNA.

Graphical abstractA series of new dinuclear zinc complexes based on bis(thiosemicarbazone) ligands has been synthesized. Their anticancer activity was screened against five cancer cell lines. One of the complexes, 6, was found to be quite cytotoxic, and as effective as adriamycin against MCF-7 and HepG2 cell lines. In spite of very different cytotoxicity, all dinuclear zinc complexes bind to DNA through electrostatic interaction without causing any significant DNA cleavage like their mononuclear counterparts.Figure optionsDownload full-size imageDownload as PowerPoint slide