Comparison of the reactivity of oxaliplatin, pt(diaminocyclohexane)Cl2 and pt(diaminocyclohexane1)(OH2)2(2+) with guanosine and L-methionine.
The initial rates of reactivity of oxaliplatin, its metabolites Pt(dach)Cl2 and Pt(dach)(OH2)2(2+) with guanosine and L-met in water, NaCl and phosphate were compared. Versus guanosine, the most reactive molecule was Pt(dach)(OH2)2(2+), about 40 fold that of oxaliplatin, the least reactive was Pt(dach)Cl2, Versus L-met, Pt(dach)(OH2)2(2+), was also the most reactive species but only about 2 fold more reactive than Pt(dach)Cl2 and oxaliplatin. Pt(dach)(OH2)2(2+) was approximately 3 fold less reactive versus methionine than guanosine whereas oxaliplatin and Pt(dach)Cl2 were about seven fold more reactive versus methionine than guanosine. Thus, the three platinum compounds oxaliplatin, Pt(dach)Cl2 and Pt(dach)(OH2)2(2+) react with L-met but only the Pt(dach)(OH2)2(2+) has a high reactivity with guanosine. Oxaliplatin, which is stable in water, has to be transformed in the presence of chloride in chloro-derivatives which are aquated to become active particularly versus guanosine. These data demonstrate that oxaliplatin has similarities with cisplatin in terms of chloride versus water coordination and in terms of dependence on chloride concentration for transformations.
Verstraete
S
S
Laboratoire de Pharmacologie et de Toxicologie, Centre Hospitalier Universitaire, Angers, France.
Heudi
O
O
Cailleux
A
A
Allain
P
P
D000970:Antineoplastic Agents / Q000737:chemistry / Q000378:metabolism; D006151:Guanosine / Q000378:metabolism*; D066298:In Vitro Techniques; D007700:Kinetics; D008715:Methionine / Q000378:metabolism*; D009944:Organoplatinum Compounds / Q000737:chemistry / Q000378:metabolism*; D000077150:Oxaliplatin
D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds; C426283:pt(diaminocyclohexane)Cl2; D000077150:Oxaliplatin; D006151:Guanosine; D008715:Methionine