Sanazole as substrate of xanthine oxidase and microsomal NADPH/cytochrome P450 reductase.
The influence of sanazole and metronidazole on cytochrome C (Cyt c(3+)) reduction in the enzyme systems xanthine/xanthine oxidase and NADPH-cytochrome P450 reductase was studied. The addition of sanazole but not metronidazole significantly increased the rate of Cyt c(3+) reduction in both enzyme systems. The Lineweaver-Burk plot of the rate of Cyt c(3+) reduction (in xanthine/xanthine oxidase system) versus sanazole concentration indicates that the apparent K(m) for sanazole is about 1.5 mM (in hypoxic medium). The results obtained suggest that xanthine oxidase and microsomal NADPH/cytochrome P450 reductase can be enzymes participating in sanazole bioactivation and manifestation of its radiosensitizing and tumoricidal activity. It is concluded that the ability of sanazole to selectively bioactivate in hypoxic tumor tissue and form immunogenic conjugates with tumor protein can be a starting-point for developing nitroazole drugs with immunomodulation anticancer properties.
Schepetkin
I A.
IA
Cancer Research Institute, 634001, Tomsk, Russia
Cherdyntseva
N V.
NV
Kagiya
V T.
VT