Synthesis and in vitro biological evaluation of three 4 '-(4-methoxyphenyl)-2,2 ':6 ',2 ''-terpyridine iridium(III) complexes as new telomerase inhibitors

There iridium(III) complexes, [Ir(3-MeO-Phtpy)Cl-3] (1), [Ir(2-MeO-Phtpy)Cl-3] (2) and [Ir(4-MeO-Phtpy)Cl-3] (3) with 4'-(3-methoxyphenyl)-2,2':6',2 ''-terpyridine (3-MeO-Phtpy), 4'-(2-methoxyphenyl)-2,2':6',2 ''-terpyridine (2-MeO-Phtpy) and 4'-(4-methoxyphenyl)-2,2':6',2 ''-terpyridine (4-MeO-Phtpy) as ligands, respectively, were synthesized and evaluated for their antiproliferative activities. In these complexes, the iridium(III) center adopts a six-coordinate distorted octahedral geometry. Among them, complex 1 exhibited the most potent activity, with IC50 values of 3.19-27.77 mu M against four cancer cell lines (BEL-7404, Hep-G2, NCI-H460 and MGC80-3 cells). Cellular mechanism studies suggested that complexes 1-3 directly targeted c-myc promoter elements and inhibited the telomerase activity. In addition, complexes 1-3 may trigger cell apoptosis via a mitochondrial dysfunction pathway. We postulated that the difference in the in vitro antitumor activities of complexes 1-3 is mainly dependent on the position of the methoxy group on the phenyl ring of the iridium ligand. (C) 2017 Elsevier Masson SAS. All rights reserved.