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 NiLCl 2 ( 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. [ABSTRACT FROM AUTHOR]