Estudo eletroanalítico da degradação química do antineoplásico raltitrexede e de sua interação com o DNA

The raltitrexede (RTX) is a folate analogue that belongs to the antimetabolite family and has antineoplastic activity, since it inhibits the thymidylate synthase (TS) enzyme. This enzyme is responsible for the synthesis of thymidine triphosphate (TTP), a nucleotide necessary forDNA synthesis. Inhibition of TS causes DNA fragmentation and consequently cell death. RTX has antineoplastic activity for a variety of solid tumors, but its main application is the treatment of advanced colorectal cancer, being approved in several countries [1] Electrochemical techniques, such as voltammetric pulse techniques, are suitable for studies of biological systems, since theyare fast, low cost and have highs electivity and sensitivity [2-4]. DNA electrochemical biosensors, using differential pulse voltammetry, has been successfully applied to investigate the interaction of DNA with anticancerdrugs[4].In this work, the chemical degradation of RTX and its interaction with dsDNA at physiological media were investigated at glassy carbon electrode byusing electrochemical techniques and DNA electrochemical biosensors. The DNA damage was detected following the changes in the oxidation peaks of guanosine and adenosine residues and monitoring the appearance of DNA oxidized products (e.g. 8-oxoguanine).RTX at physiological media is irreversibly electroxidized in twoconsecutive charge transfer reactions that are associated with the oxidation of functional groups of the electron-donor molecule,such as the amino groupand the benzene ring. RTXchemical degradation causes adecrease on the RTXanodic peak current with incubation time. Essays with the DNA electrochemical biosensor revealed only a slight decrease of the dsDNA oxidation peak with incubation time and no evidence of DNA oxidative damage. These results revealed clearly a weak interaction between RTX and dsDNA molecule, which can be associated with its lower toxicity potential when compared with others antineoplastic agents [1].