Toward overcoming cisplatin resistance via sterically hindered platinum(II) complexes

• A novel series of platinum(II) complexes with (1R,2R)-N1-benzylcyclohexane-1,2-diamine derivatives were synthesized.
• Complexes showed antitumor activity against the tested cancer cell lines.
• Complex 2 as the most potent agent has the potential to overcome cisplatin resistance.
• Complex 2 arrested SGC7901 cells in G2 and S phase, while arrested HepG2 cells in G1 phase.
• Complex 2 can induce cell apoptosis by intrinsic mitochondrial pathway.

A number of platinum(II) complexes with steric hindrance derived from (1R,2R)-N1-benzylcyclohexane-1,2-diamine derivatives were designed and prepared. Biological assay indicated that most complexes showed antitumor activity against the tested cancer cell lines, especially those with chloride anions as leaving groups had compatible or superior activity to cisplatin and oxaliplatin. Complex 2a, as the most potent agent, is also sensitive to cisplatin resistant SGC7901/CDDP cancer cell line, which has been subsequently studied by cellular uptake, flow cytometry, gel electrophoresis and western blot assays. The steric hindrance resulting from a pending 2-fluorobenzyl moiety of the ligand might be the key factor for its ability to overcome cisplatin resistant cancer cells.

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