Ring-Opened Adducts of the Anticancer Drug Carboplatin with Sulfur Amino Acids

Abstract
Reactions of the anticancer drug carboplatin (“Paraplatin”) with a variety of sulfur-containing amino acids have been investigated by 1H and 15N NMR spectroscopy and by HPLC. Thiols react very slowly and sulfur-bridged species containing four-membered Pt2S2 rings are the predominant products. In contrast, reactions with thioether ligands are much more rapid, and kinetics for the initial stages of the reaction with l-methionine have been determined (k = 2.7 × 10-3 M-1 s-1). Surprisingly, very stable ring-opened species are formed such as cis-[Pt(CBDCA-O)(NH3)2(l-HMet-S)] which has a half-life for Met-S,N ring-closure of 28 h at 310 K. A study of the formation of the analogous product for N-acetyl-l-methionine and its subsequent ring closure is reported. Reactions such as these may play a role in the biological activity of carboplatin.

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