Metronidazole is selectively toxic to anaerobic organisms. Its activation to the cytotoxic nitro-radical anion requires:

• A Aerobic oxidative metabolism by mammalian hepatic CYP3A4
• B Reductive activation by low-redox-potential electron carriers (ferredoxin/PFOR) present only in anaerobic/microaerophilic organisms ✓
• C Alkaline hydrolysis by bacterial β-lactamase enzymes
• D Phosphorylation by bacterial kinases in aerobic conditions

Explanation

Metronidazole is a prodrug that undergoes intracellular reductive activation: its nitro group accepts electrons from low-redox-potential electron carriers such as pyruvate-ferredoxin oxidoreductase (PFOR) and ferredoxin, which are present only in organisms with anaerobic (or micro-aerophilic) metabolism. The resulting reactive nitro-radical anion damages DNA by strand breaks. In aerobic environments, oxygen re-oxidises these carriers before they can reduce metronidazole, making the drug inactive in aerobes. This explains selective toxicity to Bacteroides, Clostridium, Entamoeba, Giardia, and Trichomonas.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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