Toxicity of the Mitochondrial Poison Dequalinium Chloride in a Murine Model System

Quaternary Ammonium Salts and Their Antimicrobial Potential: Targets or Nonspecific Interactions?

“…This includes pharyngeal sprays, throat lozenges, mouth washes and decongestant sprays, topical creams, gels, and ointments, as well as tablets or suppositories for vaginal application. Beside its antibacterial activity, dequalinium has been reported to exhibit an array of other biological effects such as potent antitumor activity through toxicity against mitochondria, [8][9][10][11][12] inhibition of protein kinase C, [13,14] antimalarial, [15][16][17] antitrypanosomal, [3,6] and antifungal [7] activities, inhibition of mycothiol ligase in Mycobacterium tuberculosis, [5] selective blockade of small-conductance Ca 2 + -activated K + channels, [18][19][20][21][22][23][24] and disintegration of amyloid fibrils. [25] In addition to these effects, dequalinium's toxicity has also been reported; it may cause skin necrosis if administered on intertriginous skin areas under occlusive conditions.…”

From Serendipity to Mitochondria-Targeted Nanocarriers

“…DQAsomes? The same question applies to a series of studies conducted during the early 1990s, in which dequalinium chloride at concentrations below 0.01 mM was tested for its anticarcinoma activity in xenograft models (12,18,35). How stable are DQAsomes upon dilution?…”

“…enhancing, oxidative stress and subsequently for increasing the production of ROS has been shown to induce cell death in human leukemia cells (16) and in Plasmodium berghei-infected erythrocytes (17). Thus, it seems rather surprising that such a "mitochondrial poison" (18), which even had been implicated in necrosis of the penis (19), could actually lead to the development of mitochondria-targeted pharmaceutical nanocarriers.…”

Cancer cells have distinct electrical properties that predict a susceptibility to lipophilic anions; a new cancer drug paradigm

“…This is despite rhodamine 123 being accumulated extensively by rat kidney cells, ex vivo, in an isolated kidney [79]. Dequalinium damaged the kidneys (and liver) of mice in toxicological evaluations that explored maximal dosages permissible [80]. In an Appendix to this paper I discuss in some detail why I think MKT-077 causes kidney damage.…”