Metronidazole's selective toxicity toward anaerobes and protozoal infections (e.g., Giardia, Trichomonas, Entamoeba) depends on:

• A High lipophilicity allowing passive diffusion into all cells
• B Binding to the 50S ribosomal subunit, which is unique to anaerobic bacteria
• C Direct chelation of ferrous iron in anaerobic metabolic pathways
• D Reductive bioactivation by ferredoxin/flavodoxin electron carriers present only in anaerobes/microaerophiles, forming cytotoxic nitro radical anions ✓

Explanation

Metronidazole is a prodrug; it requires reduction of its nitro group to a nitro radical anion or hydroxylamine intermediate to exert cytotoxicity. This reduction occurs only in cells with low redox potential — specifically via ferredoxin and pyruvate:ferredoxin oxidoreductase found in strict anaerobes and some microaerophilic organisms. In aerobic cells, the nitro group remains unreduced and the drug is inactive, explaining its selective toxicity.

Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.

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