Menadione

Biofilm-associated infections are typically highly antibiotic resistant and may require 100-1000-fold higher antibiotic drug concentrations. Antimicrobial blue light (aBL) alone was not particularly effective against biofilms, but the killing produced by the bactericidal mechanism of aBL (ROS generation) can be enhanced with the addition of a photosensitizer. Menadione is a lipophilic quinone that can absorb blue light and increase ROS production, including singlet oxygen and hydroxyl radicals. The addition of Menadione and blue light enhanced the killing significantly. Dark toxicity of Menadione alone was negligible and phototoxicity of Menadione was fluent- and concentration-dependent. Authors concluded that topical Menadione can significantly and safely enhance aBL therapy, providing a novel non-antibiotic therapeutic approach against MDR biofilm infections.

Fig. 1 Menadione combined with blue light eradicates drug-resistant bacteria in biofilms. (Negri L B.; et al. 2023)

MitoK3 is a mitochondria-targeted derivative of menadione (vitamin K3). It was developed as a menadione analog to potentiate the anti-cancer activity of menadione by disrupting mitochondrial function. MitoK3 was prepared by conjugating a triphenylphosphonium cation to the C3 position of menadione's naphthoquinone ring to drive selective accumulation in mitochondria. This modification caused changes in the redox properties of menadione and potentiated the mitochondrial toxicity of the parent compound.
MitoK3's mechanism of action is the result of this preferential accumulation in mitochondria where it was shown to uncouple oxidative phosphorylation and inhibit complex I-driven ATP synthesis. MitoK3 was shown to do this without opening the mitochondrial permeability transition pore (mPTP) or inducing the production of reactive oxygen species. Electrochemical studies were performed to compare the redox chemistry of MitoK3 with menadione. It was found that mitoK3 underwent reversible redox cycling similar to menadione, but had reduced oxidant properties. MitoK3 also selectively bypassed blocks to the electron transport chain at complex I/II, but not complex III. This was in contrast to menadione.

Fig. 2 Mechanism for anti-cancer activity of a novel Menadione derivative. (Teixeira J.; et al. 2018)