Synthesis, cytotoxicity, and structure-activity relationships of new oxaliplatin derivatives

In order to setup structure-activity relationships and to explore the possibilities of improving the anticancer activity of oxaliplatin, which was recently approved for combination chemotherapy of metastatic colorectal cancer, new oxatiplatin analogues have been synthesized. The cytotoxicity was determined in nine human tumor cell lines and revealed a comparable or even higher cytotoxic potency in leukemia, ovarian and colon cancer cell lines in the case of small substituents at position 4 of the cyclohexane-1,2-diamine ligand. Introduction of bigger substituents at this position and thereby increasing the steric demand of the dian-tine ligands and the lipophilicity of the oxaliplatin derivatives resulted in platinum complexes with reduced cytotoxic properties.