What is the mechanism of action of delamanid?

• A. Inhibits mycolic acid synthesis and generates reactive nitrogen species.
• B. Inhibits ribosomal protein synthesis.
• C. Inhibits RNA polymerase.
• D. Inhibits folate synthesis.

Answer: (B)

Delamanid works by blocking the production of mycolic acids, vital components of the Mycobacterium tuberculosis cell wall. It’s a prodrug that the bacterium activates via a specific F420-dependent nitroreductase, Ddn. Once activated, it releases reactive nitrogen species, notably nitric oxide, which disrupts cell-wall lipid synthesis and weakens the mycobacterial envelope. The result is inhibited formation of methoxy- and ketomycolates, leading to a bactericidal effect, especially in drug-resistant TB. This is distinct from inhibitors of ribosomal protein synthesis, RNA polymerase, or folate synthesis, which target completely different cellular processes.