Free radical induced activity of an anthracycline analogue and its MnII complex on biological targets through in situ electrochemical generation of semiquinone

Figures

• 

  Figure 1. Structure of (A) Alizarin, (B) [MnII(alz)2(H2O)2] and (C) an anthracycline anticancer drug.

• 

  Figure 2. Plot of cathodic peak current (Ipc) vs. square root of scan rate (ν) for two-electron reduction of alizarin (A) and Mn(II)-alizarin complex (B) in aqueous solution at a potential of -0.65 V and -0.75 V respectively at pH ~ 7.4.

• 

  Figure 3. Cyclic voltammogram of 0.01 mM alizarin at pH ~ 7.4 showing single step two electron reduction of the quinone in aqueous solution containing 0.12 M KCl on a glassy carbon electrode (surface area 0.1256 cm2); Scan rate 100 mV/s.

• 

  Figure 4. A scheme showing the basis for this study.

• 

  Figure 5. HPLC chromatograms obtained at 254 nm for 1 × 10−3 mol dm−3 of (A) thymine, (B) cytosine solutions that were subjected to a constant potential of -0.65 V in the presence of 1 × 10−5 mol dm−3 alizarin under de-aerated (Ar saturated) conditions. A to F indicates time in minutes for which such constant potential was applied to the solution; A: 0 min, B: 2 min, C: 4 min, D: 6 min, E: 8 min, F: 10 min.

• 

  Figure 6. Plots shown in (A), (B), (C) and (D) indicate percentage of uracil, thymine, cytosine and adenine remaining following interaction of in situ electrochemically generated species on alizarin and its MnII complex. Different experimental conditions were: nucleobase alone in absence of O2 (black circles); nucleo base alone in presence of O2 (green circles); nucleobase in presence of alizarin but absence of O2 (red circles); nucleobase in presence of alizarin and presence of O2 (blue circles); nucleobase in presence of MnII(alz)2(H2O)2 but absence of O2 (magenta circles); nucleobase in presence of MnII(alz)2(H2O)2 and presence of O2 (pink circles).

• 

  Figure 7. Fluorescence spectra of 1 × 10−3 mol dm−3 calf thymus DNA after treatment with EtBr following interaction with the products generated on the Mn(II) complex of alizarin that was subjected to reduction at constant potential (-0.75 V) in de-aerated (Argon saturated) conditions. [MnII(alz)2(H2O)2] = 3 × 10−5 mol dm−3.“a” to “e” indicates time in minutes for which the potential was applied to the solution; a: 0 min, b: 15 min, c: 30 min, d: 45 min, e: 60 min “f” denotes the spectrum of EtBr when it was excited alone i.e. in the absence of DNA at 510 nm.

• 

  Figure 8. Plots obtained for semiquinone radical anion induced modification of calf thymus DNA in the absence and presence of alizarin and the MnII complex in an argon saturated medium at pH 7.4; in absence of a compound (black circles); in the presence of alizarin (blue circles) and [MnII(alz)2(H2O)2] (red circles).