Preparation of 4-([2,2′:6′,2-terpyridin]-4′-yl)-N,N-diethylaniline NiII and PtII complexes and exploration of their in vitro cytotoxic activities

Two metal complexes of NiLCl2 (1) and [PtLCl]Cl (2) with 4-([2,2':6',2 ''-terpyridin]-4'-yl)-N,N-diethylaniline (L) were synthesized and characterized. 1 and 2 exhibited selective cytotoxicity to T-24 cells more than L, compared with the normal liver cell line (HL -7702). Various experiments showed that L,1 and 2 caused T-24 cell cycle arrest at S phase, as shown by the down -regulation of cdc25 A, cyclin A, cyclin B and CDK2 and the up -regulation of p21, p27 and p53. Furthermore, complexes 1 and 2, especially complex 2, acted as telomerase inhibitors targeting c-myc G-quadruplex DNA and triggered cell apoptosis. In addition, 1 and 2 also caused mitochondrial dysfunction. Taken together, we found that 1 and 2 exerted their cytotoxic activity mainly via inhibiting telomerase by interaction with c-myc quadruplex and disruption of mitochondrial function. (C) 2015 Elsevier Masson SAS. All rights reserved.