Copper(II) complexes of terpyridine derivatives: A footstep towards development of antiproliferative agent for breast cancer

Two copper(II) complexes with terpyridyl conjugates, [Cu(meotpy)(dmp)](NO3)2 (1) and [Cu(bitpy)(dmp)](NO3)2 (2) where meotpy, bitpy and dmp stand for methoxybenzyl terpyridine, benzimidazolyl terpyridine and dimethyl phenanthroline respectively have been synthesized and characterized. Complex 1 has also been characterized crystallographically. Both the complexes have been found to bind CT-DNA intercalatively. The ability of these complexes to bring about DNA cleavage has been analyzed using gel electrophoresis. Both complexes 1 and 2 have been found to bring about hydrolytic cleavage of DNA. The cytotoxicity of both these complexes has been tested against cancerous as well as non-cancerous cell lines. Towards non-cancerous cell line complex 2 exhibited very low toxicity. On the other hand both the complexes have been found to exhibit cytotoxic effects against cancerous cell lines. Complex 2 which has lower IC50, was found to be a potent antiproliferative agent against MCF-7 cells and was able to induce mitochondrial-mediated and caspase-dependent apoptosis with increase in G0/G1 and subsequent arrest in the S phase, in cell cycle progression. Based on this study, it is hypothesized that 2 may be a suitable candidate for further evaluation as a chemopreventive and chemotherapeutic agent for human cancer.

Graphical abstract•Two Cu(II) complexes of terpyridyl derivatives have been synthesized and both showed cytotoxic effect towards cancer cell line and less toxic effect on VERO cells.•Complex 2 whose IC50 is half of complex 1 was further examined and found that 2 undergoes apoptosis via the mitochondrial mediated pathway.Figure optionsDownload full-size imageDownload as PowerPoint slide