Synthesis, characterization and biological evaluation of six highly cytotoxic ruthenium(ii) complexes with 4'-substituted-2,2':6',2''-terpyridine.

Herein, six ruthenium(ii) terpyridine complexes, [RuCl(4-EtN-Phtpy)(DMSO)] (), [RuCl(4-MeO-Phtpy)(DMSO)] (), [RuCl(2-MeO-Phtpy)(DMSO)] (), [RuCl(3-MeO-Phtpy)(DMSO)] (), [RuCl(1-Bip-Phtpy)(DMSO)] (), and [RuCl(1-Pyr-Phtpy)(DMSO)] () with 4'-(4-diethylaminophenyl)-2,2':6',2''-terpyridine (4-EtN-Phtpy), 4'-(4-methoxyphenyl)-2,2':6',2''-terpyridine (4-MeO-Phtpy), 4'-(2-methoxyphenyl)-2,2':6',2''-terpyridine (2-MeO-Phtpy), 4'-(3-methoxyphenyl)-2,2':6',2''-terpyridine (3-MeO-Phtpy), 4'-(1-biphenylene)-2,2':6',2''-terpyridine (1-Bip-Phtpy), and 4'-(1-pyrene)-2,2':6',2''-terpyridine (1-Pyr-Phtpy), respectively, were synthesized and fully characterized. The MTT assay demonstrates that the anticancer activity of is higher than that of and more selective for Hep-G2 cells than for normal HL-7702 cells. In addition, various biological assays show that and , especially the complex, are telomerase inhibitors targeting c-myc G4 DNA and also cause apoptosis of Hep-G2 cells. With the same Ru center, the antitumor activity and cellular uptake ability of the 4-EtN-Phtpy and 1-Bip-Phtpy ligands follow the order 4-EtN-Phtpy > 1-Bip-Phtpy.