Effect of chirality in platinum drugs

摘要

Biological targets, such as proteins and nucleic acids, are chiral, therefore stereoisomers of chiral molecules interact with these targets differently and, indeed, the antitumor drug oxaliplatin contains only one enantiomer (R,R) of its 1,2-cyclohexanediamine (DACH) ligand. In this review article we illustrate the effect of chirality in platinum drugs in relation to different aspects spanning from cytotoxicity to mutagenicity, from differences in the reaction with DNA and processing of DNA lesions to gene expression and proteomic profile, to conclude with a section on the use of platinum compounds with chiral amines to investigate non-covalent interactions in adducts of platinum drugs with nucleotides and DNA. Unlike the deep understanding of the interactions at a molecular level which has allowed us to interpret the different antitumor activity and mutagenicity of DACH enantiomers and to propose an explanation for the particularly high efficacy of cisplatin toward the testis tumor, it is noted that "omics" investigations are still scanty and a reassessment of chirality effects, through molecular profiling technologies, would be timely as well as appropriate. (C) 2014 Elsevier B.V. All rights reserved.