What is the mechanism of Delamanid?

Delamanid is an anti-tuberculosis medication specifically used for treating multi-drug resistant tuberculosis (MDR-TB). Understanding the mechanism of action of Delamanid is essential for comprehending how it contributes to combating this severe form of tuberculosis.

Delamanid works by targeting the cell wall synthesis of Mycobacterium tuberculosis, the bacterium responsible for tuberculosis. The cell wall of this bacterium is crucial for its survival and virulence, making it an ideal target for antimicrobial agents. Delamanid specifically inhibits the synthesis of methoxy-mycolic and keto-mycolic acids, which are vital components of the mycobacterial cell wall. By inhibiting the production of these acids, Delamanid disrupts the integrity and function of the cell wall, ultimately leading to the death of the bacterial cell.

The mode of action of Delamanid is attributed to its active metabolite. Once administered, Delamanid undergoes a reduction process, facilitated by the enzyme deazaflavin-dependent nitroreductase (Ddn) present in Mycobacterium tuberculosis. The reduction of Delamanid generates reactive nitrogen species, which then interact with multiple targets within the bacterial cell. A prominent consequence of this interaction is the inhibition of mycolic acid synthesis, a critical component of the cell wall.

By disrupting the synthesis of mycolic acids, Delamanid weakens the cell wall, making the bacterium more susceptible to external stress and ultimately leading to cell lysis. This mechanism is particularly effective against MDR-TB strains, which have developed resistance to conventional first-line anti-TB drugs such as isoniazid and rifampicin.

Delamanid is usually administered in combination with other anti-TB medications as part of a comprehensive treatment regimen for MDR-TB. This combination therapy helps to prevent the development of further resistance and enhances the overall effectiveness of the treatment. The use of Delamanid in conjunction with other drugs helps to ensure that multiple targets within the bacterial cell are attacked simultaneously, reducing the likelihood of the bacterium developing resistance to any single agent.

In summary, Delamanid acts by inhibiting the synthesis of crucial mycolic acids in the cell wall of Mycobacterium tuberculosis, leading to the disruption of cell wall integrity and bacterial death. Its unique mechanism, involving the generation of reactive nitrogen species and subsequent inhibition of mycolic acid synthesis, makes it a valuable addition to the arsenal of drugs used to treat multi-drug resistant tuberculosis. This targeted approach not only helps in effectively combating MDR-TB but also in reducing the risk of further resistance development, making Delamanid a crucial component in the fight against this challenging infectious disease.