摘要：A series of group-10 metal complexes 1-14 of oxoisoaporphine derivatives were designed and synthesized. 1-14 were more selectively cytotoxic to Hep-G2 cells comparing with normal liver cells. In vitro cytotoxicity results showed that complexes 1-6, 7, 8, 10 and 11, especially 3, were telomerase inhibitors targeting c-myc, telomeric, and bcl-2 G4s and triggered cell senescence and apoptosis; they also caused telomere/DNA damage and S phase arrest. In addition, 1-6 also caused mitochondrial dysfunction. Notably, 3 with 6-amino substituted ligand L(a) exhibited less side effects than 6 with 8-amino substituted ligand L(b) and cisplatin, but similar tumor growth inhibition efficacy in BEL-7402 xenograft model. Complex 3 has the potential to be developed as an effective anticancer agent.
