Prontosil (the first sulfonamide): in which setting is it an effective antibacterial agent, and why was this discovery pivotal?

Introduction:
Prontosil, a red azo dye discovered in the 1930s, ushered in the antibiotic era. Its paradox—active in vivo but inactive in vitro—transformed chemotherapeutic research. This question tests whether you know where Prontosil works and the metabolic basis for its activity.

Given Data / Assumptions:

• Prontosil shows antibacterial efficacy in animals and humans.
• It does not inhibit bacterial growth in standard cell-free culture tests.
• Metabolic activation in the host is required for antibacterial effect.

Concept / Approach:
Prontosil is a prodrug. In vivo, it is metabolized (via azo-reduction) to release sulfanilamide, the true active antibacterial that inhibits folate synthesis (dihydropteroate synthase). Since cell-free culture tests lack this metabolic conversion, Prontosil appears inactive in vitro, explaining the early experimental discrepancy.

Step-by-Step Solution:
Recall Prontosil’s historical observation: cures infections in animals but fails in test tubes. Identify prodrug nature: metabolic cleavage yields sulfanilamide. Connect mechanism: folate pathway inhibition blocks bacterial growth in vivo. Choose the option indicating in vivo (animals) efficacy only.

Verification / Alternative check:
Subsequent use of sulfanilamide itself in vitro demonstrates robust antibacterial activity, confirming Prontosil’s prodrug status.

Why Other Options Are Wrong:

• In vitro activity: Absent without metabolic activation.
• Both in vivo and in vitro: Contradicted by early experimental data.
• Not used as antibacterial: Historically pivotal as first widely used systemic antibacterial.

Common Pitfalls:
Assuming all antibiotics show direct in vitro activity; some agents require bioactivation within the host.

Final Answer:
an effective antibacterial when used in animals — Prontosil is active in vivo due to metabolic conversion to sulfanilamide.