Fig. 7. Summary of the action of HM2-16F at the level of the respiratory chain.

HM2-16F inhibits cytochrome bd and, to a lesser or indirect extent, the F₁F_o-ATP synthase. Disruption of quinol regeneration can affect the primary dehydrogenases of the respiratory chain leading to dysregulated regeneration of reducing equivalents that can lead to a systemic failure of cellular redox reactions. The addition of Q203 (or TB47), direct inhibitors of the cytochrome bcc-aa₃ oxidase branch, removes the only alternative pathway that mycobacteria can use to escape this inhibition of oxygen consumption leading to cell death.