F. Dufrasne and M. S. Galanski Pages 2781 - 2794 ( 14 )
The origin of activity differences between stereoisomers of anticancer platinum(II) complexes chelated with chiral diamine ligands has been almost exclusively explained by diastereoselective interactions with DNA. Although this model has been widely accepted in vitro and in vivo experiments showed some conflicting results, leading to the conclusion that other biomolecules might be responsible for this stereoselectivity as well. These compounds, called bionucleophiles, are in most instances amino acids or proteins present in biological fluids. As these chiral molecules are very reactive towards the platinum complexes, they may contribute to stereoselectivity, but also to resistance and toxicity. This review gives a general survey of chiral platinum(II) complexes and their interactions with DNA. The bionucleophiles which have been identified and the consequences of their reaction with platinum(II) complexes are discussed. Analytical techniques used to investigate interactions between established and potential chiral platinum drugs and bionucleophiles are presented.
Stereoisomers,cancer,platinum complexes,bionucleophiles,analysis,stereoselectivity,diaminocyclohexane
, Institut de Pharmacie, Universite Libre de Bruxelles CP205/5, Campus Plaine, 1050, Brussels, Belgium.