Synthesis, crystal structure, cytotoxicity and action mechanism of Zn(II) and Mn(II) complexes with 4-([2,2′:6′,2′′-terpyridin]-4′-yl)-N,N-diethylaniline as a ligand

Two metallo-complexes, [Mn(L)2]·2ClO4 (1) and [Zn(L)(NO3)2] (2), with 4-([2,2′:6′,2′′-terpyridin]-4′-yl)-N,N-diethylaniline (L) as the ligand were synthesized and characterized. They exhibited selective cytotoxicity against BEL-7404, SK-OV-3, MGC80-3, and T-24 cell lines with IC50 values in the micromolar range (1.28–14.86 μM). Further mechanistic studies showed that complexes 1 and 2 inhibited telomerase by interacting with c-myc G-quadruplex DNA and induced cell cycle arrest at the S phase. They also caused the down-regulation of cdc25 A, cyclin A, cyclin B and CDK2, and the up-regulation of p21, p27 and p53.