TY - JOUR
T1 - Reductive activation of potential antitumor bis(aziridinyl)benzoquinones by xanthine oxidase: Competition between oxygen reduction and quinone reduction
AU - Lusthof, K.J.
AU - Richter, W.
AU - de Mol, N.J.
AU - Janssen, L.H.M.
AU - Verboom, Willem
AU - Reinhoudt, David
PY - 1990
Y1 - 1990
N2 - The reduction of a series of 2,5-bis(1-aziridinyl)-1,4-benzoquinone (BABQ) derivatives with various 3,6 substituents by the enzyme xanthine oxidase has been studied. The reduction rate has been assayed by measuring the rate of reduction of cytochrome c, which is very efficiently reduced by reduced BABQ species. Under nitrogen, the reduction rate correlated with the quinone reduction potential and steric parameters. Comparing reduction rates under nitrogen and air demonstrates that at BABQ concentrations > 25 μm the competition for electrons from xanthine oxidase between oxygen and the BABQ derivative is dominated by the latter. This is also confirmed by the effect of superoxide dismutase (SOD): in the presence of a BABQ derivative, cytochrome c reduction can be totally inhibited by SOD, although the required amount of SOD depends on the redox potential of the quinones. This indicates that SOD causes the equilibrium between semiquinone and superoxide to shift, resulting in a decrease of the semiquinone concentration. It is concluded that reduction by xanthine oxidase is a simple and effective method for reducing aziridinylbenzoquinones.
AB - The reduction of a series of 2,5-bis(1-aziridinyl)-1,4-benzoquinone (BABQ) derivatives with various 3,6 substituents by the enzyme xanthine oxidase has been studied. The reduction rate has been assayed by measuring the rate of reduction of cytochrome c, which is very efficiently reduced by reduced BABQ species. Under nitrogen, the reduction rate correlated with the quinone reduction potential and steric parameters. Comparing reduction rates under nitrogen and air demonstrates that at BABQ concentrations > 25 μm the competition for electrons from xanthine oxidase between oxygen and the BABQ derivative is dominated by the latter. This is also confirmed by the effect of superoxide dismutase (SOD): in the presence of a BABQ derivative, cytochrome c reduction can be totally inhibited by SOD, although the required amount of SOD depends on the redox potential of the quinones. This indicates that SOD causes the equilibrium between semiquinone and superoxide to shift, resulting in a decrease of the semiquinone concentration. It is concluded that reduction by xanthine oxidase is a simple and effective method for reducing aziridinylbenzoquinones.
KW - IR-72902
U2 - 10.1016/0003-9861(90)90561-C
DO - 10.1016/0003-9861(90)90561-C
M3 - Article
SN - 0003-9861
VL - 277
SP - 137
EP - 142
JO - Archives of biochemistry and biophysics
JF - Archives of biochemistry and biophysics
IS - 1
ER -