884 V) to that of guanosine (approximately +0.80 V vs. Ag/AgCl), a DNA-constituent base, it was possible to observe a positive interaction, which was indicated by the presence of the waves of guanosine and adenosine, using a very low concentration of QPhNO2 ( Fig. 9A and B) due to solubility problems. The positive interaction between QPhNO2 and ssDNA in solution is depicted in Fig. 10. Signals associated with the oxidation of the guanine (G) and adenine (A) bases (+0.83 V and +1.16 V vs. Ag/AgCl 0.1 M, respectively) in ssDNA were very intense.

Z-VAD-FMK concentration However, in the presence of QPhNO2, the current intensity of the oxidation peaks decreased in a concentration-dependent manner until the signals leveled out (Fig. 10B and C). Increasing the concentration was precluded by dissolution problems, with the precipitation of QPhNO2. The oxidation potentials of guanine and adenine were kept nearly constant. A different behavior (currents related to the oxidation of guanine and adenine remained practically unaltered at concentrations up to 200 μM) ATM/ATR inhibitor review was reported for nor-beta (Cavalcanti et al., 2011) in studies with ssDNA, and these results suggest that those

compounds do not damage DNA directly (Brett et al., 2002, de Abreu et al., 2002a and de Abreu et al., 2002b). The positive correlation between the electrochemical and pharmacological experiments can be expanded using already reported data obtained from doxorubicin analogs. The interaction of dsDNA (calf thymus) and daunorubicin in solution and on the electrode surface was previously studied using cyclic voltammetry and particularly by constant-current chronopotentiometric stripping analysis using carbon paste electrodes, which revealed the intercalation of this drug between the base pairs in dsDNA (Wang et al., 1998). Adriamycin, a cancerostatic anthracycline antibiotic, causes considerable

tumor cell death, together with the induction of breaks in single- and double-stranded DNA. The interaction of adriamycin with DNA was also investigated using an electrochemical DNA-biosensor. Its intercalation in DNA disrupts the double helix, and the detection of guanine and 8-oxoguanine could mimic a possible mechanism for the in vivo adriamycin drug action ( Piedade et al., mTOR inhibitor 2002). Recently, Cavalcanti and coworkers reported the positive interaction between doxorubicin and ssDNA ( Cavalcanti et al., 2011). As previously shown with respect to DNA, electrochemical studies indirectly allow evidencing the generation of ROS. Experiments performed in the presence of oxygen showed that QPhNO2 reacts faster with oxygen than nor-beta and provokes a greater release of ROS. These findings corroborate with those obtained by flow cytometry. The underlying rationale for this fact may be the structure of the reduced nitroquinone (de Souza et al., 2010 and Hernández et al., 2008). The redox-cycling of quinones may be initiated by either a one- or two-electron reduction.