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

<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

Study on Antitumor Platinum(II) Complexes of Chiral Diamines with Dicyclic Species as Steric Hindrance

A series of platinum­(II) complexes, characteristic of chiral <i>trans</i>-bicyclo­[2.2.2]­octane-7,8-diamine as ligand possessing dicyclic steric hindrance, were designed and synthesized. Biological evaluation showed that almost all complexes had cytotoxic activity against the tested cancer cell lines, among which most of chiral (<i>R</i>,<i>R</i>)-enantiomeres had stronger cytotoxicity than their (<i>S</i>,<i>S</i>)-counterparts, and <b>2a</b>, [<i>trans</i>-bicyclo­[2.2.2]­octane-7<i>R</i>,8<i>R</i>-diamine]­(oxalato-<i>O</i>,<i>O</i>′)­platinum­(II), is the most effective agent. Significantly, its counterpart, <b>2b</b>, was much more sensitive to cisplatin resistant SGC7901/CDDP cancer cell line at a higher degree than <b>2a</b>. Docking study and agarose gel electrophoresis revealed that the interaction of <b>2a</b> with DNA was similar to that of oxaliplatin. Western blot analysis demonstrated that <b>2a</b> could induce a better effect than cisplatin on a mitochondrial-dependent apoptosis pathway. Kinetic study indicated that the dicyclic ligand can accelerate the reaction rate of the complex