Pulse Radiolysis Study of Aqueous Solution Reactivity of Transient Species of Biological Interest: Reactions with Various Substrates

Summary

We studied by pulse radiolysis three aspects of the oxydoreduction of three antitumour drugs whose mechanisms of action imply one-electron oxidative or reductive activations. The three antitumour drugs were BD40, daunurubicin, and mitonycin C.

We showed that when BD 40 is oxidized by OH free radicals the resulting BD 40 free radical reacts rapidly with superoxide anions.

When daunorubicin is intercalated in a protein, apo-riboflavin binding protein, COO-free radicals reduce both the antibiotic and a disulfide bond of the protein. However we had indications of intramolecular electron transfer between the protein and the semiquinone daunorubicin free radical.

The comparison between the reduction of mitanycin C with and without DMA allowed to identify the active transient which reacts specifically with DNA.

For each drug a kinetic scheme is proposed and the rate constants are determined.

Résumé

Un article précént (Jonah, ce Congrès) a souligné l’intégrt de la méthodé de la radiolyse pulsée pour l’étude de la réactivite des espèces à duréa de vie courte. Nous avons appliqué cette méthode à l’étude cinétique de l’oxydo-réduction de trois médicaments antitumoraux dont le mécanisme d’action, in vivo, est supposé être déclenché par un échange monoélectronique. Dans ce cas, des transitories radicalaires sont donc impliqués dans le déroulement de leurs réactions.