Electrochemical behaviour of anticancer drug lomustine and in situ evaluation of its interaction with DNA

Publication date: Available online 25 July 2019Source: Journal of Pharmaceutical and Biomedical AnalysisAuthor(s): Paulina Andréa V. de Carvalho, Ilanna Campelo Lopes, Elizaura Hyeda C. Silva, Evellin Enny S. Bruzaca, Hugo José Chaves, Mayara Ingrid S. Lima, Auro Atsushi TanakaAbstractElectrochemical techniques were used to investigate the behavior of lomustine (CCNU) and its degradation in aqueous solution at a glassy carbon electrode (GCE). The in situ interaction of CCNU and chemically degraded CCNU (cdCCNU) with dsDNA was then investigated in dsDNA incubated solutions, using dsDNA electrochemical biosensors and comet assays. CCNU undergoes electrochemical reduction in two irreversible, diffusion-controlled, and pH-dependent redox processes, each with transfer of two electrons and one proton. At pH ≥ 10.1, the peak potential for the two processes was essentially pH-independent and involved only one electron. A mechanism was proposed for the reduction of CCNU in a neutral medium. In addition, it was found that CCNU underwent spontaneous degradation during incubation in aqueous solution, without the formation of electroactive degradation products. The degradation process was faster in basic media. Moreover, this pro-drug interacted with the DNA. Its metabolite(s) initially caused condensation of the double helix chains, followed by the unwinding of these chains. In addition, free guanine (Gua) was released from the dsDNA and oxidative damage to the DNA by the CCNU me...
Source: Journal of Pharmaceutical and Biomedical Analysis - Category: Drugs & Pharmacology Source Type: research