Preparation and ESR spectroscopic characterization of the zinc(II) and cadmium(II) complexes of streptonigrin semiquinone1A preliminary account of portions of this work has been presented at the 14th International Conference on Radical Ions, Uppsala, Sweden, June 1–5, 1996.1

Antitumour Quinones

“…But although the drug interacts with metal ions and its DNA binding is clearly enhanced in the presence of metal ions [121][122][123][124], the exact function of these species has not yet been fully understood. It has been proposed that they either are implicated in the catalytic formation of DNA-damaging ROS or that they act as delivery agents of streptonigrin or streptonigrin semiquinone to DNA via electrostatic interactions [125][126][127]. The rings A,B and C including the quinone moiety contain the key functional groups required for biological activity.…”

Ruthenium Complexes of Analogues of the Antitumor Antibiotic Streptonigrin

“…[5][6][7][8] However, in contrast to other well-characterized aminoquinone antitumor antibiotics (eg., daunomycin, mitomycin), the mechanism of DNA strand cleavage is unique in its reliance on metal ions. [9][10][11] While the exact role of transition metal ions in the mechanism of action of streptonigrin is still not fully understood, 12 it has been proposed that metals function as delivery agents of streptonigrin or reduced streptonigrin to DNA via an electrostatic interaction [12][13][14] and/or that they catalyze the production of the DNA-damaging species. 8,15,16 Because of the important role of transition metal ions in the mechanism of antitumor action of streptonigrin, the effects of a number of metal ions on the properties of streptonigrin have been reported.…”

“…Streptonigrin is a functionalized 7-aminoquinoline-5,8-dione that is highly active against a variety of human cancers. − Extensive in vitro studies suggest that DNA is the principle cellular target responsible for anticancer activity and that this activity is directly related to streptonigrin-mediated DNA strand scission. − However, in contrast to other well-characterized aminoquinone antitumor antibiotics (eg., daunomycin, mitomycin), the mechanism of DNA strand cleavage is unique in its reliance on metal ions. − While the exact role of transition metal ions in the mechanism of action of streptonigrin is still not fully understood, it has been proposed that metals function as delivery agents of streptonigrin or reduced streptonigrin to DNA via an electrostatic interaction − and/or that they catalyze the production of the DNA-damaging species. ,, …”

The effect of metal ions on the electrochemistry of the antitumor antibiotic streptonigrin

“…The structure and lifetime of SN semiquinone is highly influenced by solvation and pH; there is minimal electron density on rings C and D and the electron is localized on the oxygen atom adjacent to the amino group in ring A (as shown in Fig. 6) [29]. Complexation of SN ÅÀ with one equivalent of Zn(II) or Cd(II) significantly changes the electron distribution in the quinoline rings, shifting the electron density to the pyridine portion of the quinoline ring and does not involve delocalization of the unpaired electron onto the metal ion [29].…”

“…6) [29]. Complexation of SN ÅÀ with one equivalent of Zn(II) or Cd(II) significantly changes the electron distribution in the quinoline rings, shifting the electron density to the pyridine portion of the quinoline ring and does not involve delocalization of the unpaired electron onto the metal ion [29]. The positive shift in E pa values of SN ÅÀ in solution with metal ions corresponds to a stabilization of SN ÅÀ with respect to SN, consistent with the metal ion stabilizing the local negative charge of the ligand.…”