The Relation Between Stereochemistry and Biological Activity of Platinum(II)
Complexes Chelated with Chiral Diamine Ligands: An Intricate Problem+
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.
Dufrasne
F
F
Pharmaceutical Organic Chemistry, CP 205/5, Pharmacy, Université Libre de Bruxelles, 1050, Brussels, Belgium.
Galanski
M S
MS
Institute of Inorganic Chemistry, University of Vienna, Waehringer Str. 42, A-1090 Vienna, Austria
D000818:Animals; D003959:Diamines / Q000737:chemistry* / Q000378:metabolism*; D006801:Humans; D008024:Ligands; D009944:Organoplatinum Compounds / Q000737:chemistry / Q000378:metabolism; D017671:Platinum Compounds / Q000737:chemistry* / Q000378:metabolism*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D003959:Diamines; D008024:Ligands; D009944:Organoplatinum Compounds; D017671:Platinum Compounds