EXAFS structural study of platinum-based anticancer drugs degradation in presence of sulfur nucleophilic species.
Three platinum complexes, cisplatin, carboplatin and oxaliplatin are currently used worldwide. Investigation of their main structural modifications in presence of sulfur nucleophiles is of particular interest because of the implication of thiol and thioether groups in biochemical mechanism of action, resistance mechanism and in vivo or in vitro detoxification. We present the main structural results we have obtained concerning the reaction of these drugs with diverse sulfur nucleophiles (cysteine, glutathione, methionine, thiosulfate and thiocyanate), monitored in solution or as precipitates by EXAFS spectroscopy. The reactivities of the carboxylate and amine ligands of both carboplatin and oxaliplatin are compared, on the basis of first-coordination sphere modeling. Among the new results of this EXAFS study, we present the first observation of oxaliplatin diaminocyclohexane ligand displacement by sulfur nucleophiles.
Provost
Karine
K
Institut de Chimie et des Matériaux Paris Est, ICMPE/SAX, UMR 7182 CNRS-Université Paris 12, PRES Paris Est, 2 à 8 Rue Henri Dunant, 94320 Thiais, France. provost@univ-paris12.fr
Bouvet-Muller
Diane
D
Crauste-Manciet
Sylvie
S
Moscovici
Jacques
J
Olivi
Luca
L
Vlaic
Gilberto
G
Michalowicz
Alain
A
D000970:Antineoplastic Agents / Q000737:chemistry*; D009944:Organoplatinum Compounds / Q000737:chemistry*; D013052:Spectrometry, X-Ray Emission; D013455:Sulfur / Q000737:chemistry*
D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds; D013455:Sulfur