Reductive bioactivations

Walton Ml, Wolf CR, Workman P (1992) The role of cytochrome P450 and cytochrome P450 reductase in the reductive bioactivation of the novel benzotriazine di-N-oxide hypoxid cytotoxin 3-amino-1,2,4-benzotriazine-1,4-dioxide (SR 4233, WIN 59075) by mouse liver. Biochim Pharmacol 44 251-259... 

The following examples illustrate the bioprecursor-prodrug approach, although the intentional use of bioprecursor design is relatively recent and, in some cases, there are some doubts about the prospective or the retrospective character of the design. The hrst examples relate to oxidative bioactivations they are followed by examples of reductive bioactivations and dually by non-redox reactions. Often, however, the active species results from a cascade of metabolic reactions involving oxidative as well as reductive processes, complicated by hydrolytic reactions or hydration-dehydration sequences. 

FIGURE 36.35 Mixed oxidative/reductive bioactivation of dioxolanes. 

F Bioactivation of cyclophosphamide Reductive Bioactivations A Reductive bioactivation of nitrogen mustards... 

B Reductive bioactivation of omeprazole Mixed Bioactivation Mechanisms... 

Mechanisms Metronidazole is an imidazole derivative with activity against protozoa and bacteria. The drug undergoes a reductive bioactivation of its nitro group by ferredoxin (present in anaerobic parasites) to form reactive cytotoxic products that interfere with nucleic acid synthesis. 

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