Synthesis, antiproliferative activity and DNA binding study of mixed ammine/cyclohexylamine platinum(II) complexes with 1-(substituted benzyl) azetidine-3, 3-dicarboxylates

A novel series of ammine/cyclohexylamine platinum(II) complexes with 1-(substituted benzyl) azetidine-3, 3-dicarboxylates as leaving groups have been synthesized and characterized. All complexes were characterized by elemental analysis, IR, 1H NMR, and ESI-MS spectra. The in vitro antiproliferative activities of the platinum-based compounds have been investigated against several human cancer cell lines, indicating that complexes 1 and 11 showed comparable cytotoxicity to those of cisplatin and oxaliplatin against four cell lines, superior to that of carboplatin. The results of drug safety evaluation (acute toxicity study) showed that complex 11 was much less toxic than cisplatin and oxaliplatin. Flow cytometry and agarose gel electrophoresis studies revealed that both complexes 1 and 11 induced apoptosis of tumor cells and demonstrated the binding affinity of complexes with pET22b plasmid DNA.

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► Ammine/cyclohexylamine Pt (II) complexes with 3, 3-dicarboxylazetidine derivatives.
► Two complexes showed high cytotoxicity close to cisplatin and oxaliplatin.
► Acute toxicity of the most active complex was lower than that of oxaliplatin.
► Compounds induced death of tumor cell analogous to cisplatin.
► Two active complexes displayed higher DNA cleavage capability than cisplatin.