Electrochemical formation of the adduct between antitumor agent C-1311 and DNA nucleoside dG

Metabolic oxidative activation of C-1311 antitumor drug is considered to be a prerequisite process influences the antitumor effect of this agent. Such activation was shown to result in the covalent binding of C-1311 with DNA in the tumour cells. To elucidate the molecular mechanism of C-1311 oxidative activation the investigations on the electrochemical oxidation of this compound have been included. In this work we have focus our studies on the search for the products of this reaction and on the detection of any adduct between C-1311 and DNA. Cyclic voltammetry and controlled-potential electrolysis were employed for the study of C-1311 alone and in the presence of dG, the most probable target for C-1311 at the DNA core. The products of exhausted electrolysis of C-1311 were analysed by HPLC with multidiode array detection and ESI-mass spectroscopy. It has been shown that two of them, E1 and E2, were exactly alike to C1 and C2, the identified earlier products obtained after enzymatic activation. The new product was found in the chromatograms collected after the electrolysis of C-1311 in the presence of dG. Its chromatographic and spectral properties allowed us to suppose that it could be the adduct of C-1311 with DNA, which has never been found during the enzymatic activation of C-1311 with dG. Keywords: Imidazoacridinone antitumor agent, C-1311 antitumor drug, Electrochemical synthesis, DNA adduct formation, Voltammetry