Two platinum(II) complexes [Pt(L)(DMSO)Cl] (1) and [Pt(L)(pn)]Cl (2) with 5-bromo-oxoisoaporphine (H-L) were synthesized. We found that the two new platinum(II) complexes were more selective for Hep-G2 tumor cells than for normal cells (HL-7702, WI-38 and L-o2 cell lines). 5-Bromine-oxoisoaporphine platinum(II) complex 2 was a telomerase inhibitor targeting c-myc G4, and it triggered Hep-G2 cell apoptosis more potently than complex 1. Moreover, they induced cell apoptosis via disruption of mitochondrial functions. Significantly increased ROS level, loss of Δψ, decrease of bcl-2 level, and increase of some of the mitochondria-initiated apoptosis protein levels (including bax, Cyt C, caspase-3, caspase-9, and apaf-1) were observed in Hep-G2 cells. In brief, complexes 1 and 2 triggered Hep-G2 cell apoptosis mainly through inhibiting telomerase activity by interacting with c-myc promoter elements and disruption of mitochondrial pathway. Our results also showed the effects of second ligands on the in vitro antitumor activity in the order of pn > Cl and DMSO.

合成了两种具有5-溴-氧代异阿哌芬（HL）的铂（II）配合物[Pt（L）（DMSO）Cl]（1）和[Pt（L）（pn）] Cl（2）。我们发现，这两种新的铂（II）配合物对Hep-G2肿瘤细胞的选择性比对正常细胞（HL-7702，WI-38和L-o2细胞系）的选择性更高。5-溴-氧代异阿吗啡铂（II）复合物2是靶向c-myc G4的端粒酶抑制剂，它比复合物1更有效地触发Hep-G2细胞凋亡。而且，它们通过线粒体功能破坏。观察到ROS水平显着升高，Δψ降低，bcl-2水平降低以及线粒体启动的某些凋亡蛋白水平的升高（包括bax，Cyt C，caspase-3，caspase-9和apaf-1）。在Hep-G2细胞中 简而言之，复合物1和2主要通过与c-myc启动子元件相互作用和抑制线粒体途径而抑制端粒酶活性，从而触发Hep-G2细胞凋亡。我们的结果还显示了第二种配体对体外抗肿瘤活性的影响，其顺序为pn> Cl和DMSO。