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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.

Preparation of 6/8/11-Amino/Chloro-Oxoisoaporphine and Group-10 Metal Complexes and Evaluation of Their in Vitro and in Vivo Antitumor Activity