Synthesis and biological evaluation of water-soluble trans-[bicyclo[2.2.2]octane-7R,8R-diamine]platinum(II) complexes with linear or branched alkoxyacetates as leaving groups

Four platinum(II) complexes, trans-[bicyclo[2.2.2]octane-7R,8R-diamine]bis(alkoxyacetato-O,O') platinum(II) (alkoxyacetate=methoxyacetate (2), ethoxyacetate (3), isopropoxyacetate (4), and tert-butoxyacetate (5)) were synthesized and spectrally characterized. The cytotoxicity of these water-soluble complexes was evaluated by CCK-8 assay in vitro against HCT-116, HepG-2, and A549 cancer cell lines. Most of the complexes had cytotoxic activity against the tested cancer cell lines. Among them, 3 showed more potent antitumor effect than cisplatin or oxaliplatin. Complex 3 could cause HCT-116 cell line death based on an apoptotic pathway since it has a dicyclic moiety similar to 1R,2R-diaminocyclohexane in oxaliplatin. Agarose gel electrophoresis on the interaction between 3 and DNA indicated that it has different behavior from that of cisplatin or oxaliplatin, which has a high correlation with the ligand used.