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.

• 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 as PowerPoint slide