Biomolecular dynamics and electron spin resonance spectra of copper complexes of antitumour agents in solution

Abstract

For the purpose of developing new antitumour agents which are more efficacious and have less generalized toxicity than existing ones, the free-radical generation and metal complexation of well known anticancer agents have been studied. Copper(II) ion complexes are readily formed with several members of a class of hydroxyurea derivatives which are known to be effective ribonucleotide reductase inhibitors. E.s.r. measurements and u.v.–visible titration illustrate weak binding for 3,4-dihydroxybenzohydroxamic acid and tight binding in complex formation for gallohydroxamic acid and 2,3,4-trihydroxybenzohydroxamic acid. These data were used in a preliminary investigation of cytotoxicity, and the results are consistent with single phase cell cycle killing.