A selected chemical library of six platinum(II) complexes having 1,2-bis(aminomethyl)carbobicyclic ligands were synthesized after a rational design in order to evaluate their antiproliferative activity and the structure-activity relationships. The cytotoxicity studies were performed using cancer cell lines sensitive (A2780) and resistant (A2780R) to cisplatin. Excellent cytotoxicity was observed for most of complexes, which presented better resistance factors than cisplatin against the A2780R cell line. The interaction of these complexes with DNA, as the target biomolecule, was evaluated by several methods: DNA-platinum binding kinetics, changes in the DNA melting temperature, evaluation of the unwinding angle of supercoiled DNA, evaluation of the interstrand cross-links, and replication mapping. The kinetics of the interaction with glutathione was also investigated to better understand the resistant factors observed for the new complexes.

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Applied chemistry Z 0300 Platinum Complexes with Cytotoxic Activity: Models for Structure-Activity Relationship Studies -[162 refs.]. -(DE MIER-VINUE, J.; MONTANA, A. M.; MORENO, V.; Met. Compd. Cancer Chemother. 2005, 47-154; Dep. Quim. Org., Univ. Barcelona, E-08028 Barcelona, Spain; Eng.) -Meier 09-277

Two 1,4-diamine ligands were synthesized having 1,2bis(aminomethyl)-cyclohexane and 1,2-bis(aminomethyl)-benzene structures. The two ligands have different electron density in the six-membered ring: a cyclohexane versus a phenyl ring. The organic synthesis of the ligands was carried out by synthetic pathways of seven and four steps, respectively, starting from 1,2,3,6-tetrahydrophthalic anhydride and diethyl phthalate. The coordination of platinum to these ligands afforded platinum(II) complexes which are analogue to the clinical drug cisplatin but form a seven-membered chelate ring. The interaction of the platinum compounds with