A glucose derivative as natural alternative to the cyclohexane-1,2-diamine ligand in the anticancer drug oxaliplatin?

Having oxaliplatin as archetype, several platinum complexes with a carbohydrate moiety resembling the cyclohexane-1,2-diamine ligand of oxaliplatin have been prepared. As leaving groups the anionic ligands iodide, oxalate and malonate were utilized and for comparison purposes the chloro complex was employed. All compounds were characterized by elemental analysis, nuclear magnetic resonance spectroscopy and electrospray mass spectrometry. The crystal structure of (SP-4-3)-diodo(2,3-diamino-2,3-dideoxy-D-glucose-kappa N-2,N')platinum(II) was determined by X-ray diffraction. the affinity toward dGMP was assayed by capillary electrophoresis,revealing that the chloro complex shows the highest reactivity, followed by the iodo complex. In contrast the binding kinetics of the dicarboxylato complexes are slower with the malonato complex being the least cytotoxicity in two of four human cancer cell lines as determined by means of the MTT assay. In three of the four cell lines, the chloro and the malonato complex are the most and the least active of the carbohydrate-Pt complexes, respectively, wit IC50 values differing only by factors of up to 3.2. Cytotoxicity of the chloro complex is one to two orders of magnitude lower than that of oxaliplatin, but still comparable to that of carboplatin in two of the four cell lines.