Delamanid, another novel anti-TB drug for MDR-TB, inhibits methoxy-mycolic acid and keto-mycolic acid synthesis. What is the activated intermediate responsible for its bactericidal effect?

• A Delamanid is activated by KatG catalase-peroxidase similar to isoniazid
• B Delamanid is a prodrug activated by deazaflavin-dependent nitroreductase (Ddn) in Mycobacterium, generating reactive intermediates (des-nitro-imidazo-oxazole) that kill the bacteria ✓
• C Delamanid requires pyrazinamidase activation and acts only in acidic environments
• D Delamanid undergoes spontaneous hydrolysis to active nitroso compounds in mycobacterial cytoplasm

Explanation

Delamanid is a nitroimidazo-oxazole prodrug that requires bioactivation by the mycobacterial deazaflavin-dependent nitroreductase (Ddn, encoded by the Rv3547 gene). Ddn transfers electrons from the F420 coenzyme to delamanid, generating reactive des-nitro-imidazo-oxazole metabolites that inhibit the synthesis of methoxy-mycolic acids and keto-mycolic acids in the cell wall. Resistance occurs through mutations in Ddn or the F420 biosynthetic genes (fbiA, fbiB, fbiC). The mechanism parallels metronidazole activation in anaerobes — both require nitroreduction for activity.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.