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

Abstract

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