Sanazole as substrate of xanthine oxidase and microsomal NADPH/cytochrome P450 reductase

I. A. Schepetkin, N. V. Cherdyntseva, V. T. Kagiya

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10 Citations (Scopus)

Abstract

The influence of sanazole and metronidazole on cytochrome C (Cyt c3+) 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 c3+ reduction in both enzyme systems. The Lineweaver-Burk plot of the rate of Cyt c3+ reduction (in xanthine/xanthine oxidase system) versus sanazole concentration indicates that the apparent Km 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.

Original languageEnglish
Pages (from-to)119-127
Number of pages9
JournalPathophysiology
Volume8
Issue number2
DOIs
Publication statusPublished - 2001
Externally publishedYes

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Keywords

  • Cytochrome P450 reductase
  • Hypoxia-selective agents
  • Sanazole
  • Xanthine oxidase

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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