Glycolysis as a target for the design of new anti-trypanosome drugs

https://research.vu.nl/ws/files/2792130/115152.pdf

What Controls Glycolysis in Bloodstream Form Trypanosoma brucei

Human African trypanosomiasis (HAT), or sleeping sickness, is currently on the rise. HAT develops in two stages, the first involving the hemolymphatic system, and the second, the neurological system. Left untreated, HAT is invariably fatal. There have been no therapeutic advances in more than 40 years. Stage 1 can be treated with pentamidine and suramin, but stage 2 can only be treated with melarsoprol, a toxic arsenic derivative that has a 2-12% incidence of fatal side-effects (encephalopathy). Eflornithine has never achieved widespread use because it is difficult to administer under field conditions. Nifurtimox has been used successfully in the treatment of American trypanosomiasis, or Chagas disease, but only in small studies or as a compassionate use treatment. There is little research and development for new drugs in this area: only one prodrug is in the clinical development phase, a pentamidine analog that offers hope for the replacement of injectable pentamidine with an orally administered drug. Current efforts appear to be focused on reevaluating older drugs. A course of treatment with melarsoprol for 10 days at 2.2 mg/kg/day is now in the multicenter evaluation phase. Orally administered eflornithine is also slated for reevaluation. In addition, studies of drug combinations are recommended to determine possible combined or synergistic effects and find ways to reduce toxicity.

Treatment perspectives for human African trypanosomiasis.

Class I aldolases: substrate specificity, mechanism, inhibitors and structural aspects

Recent advances in identifying and validating drug targets in trypanosomes and leishmanias

Inhibition of the glycolytic enzymes in the trypanosome: an approach in the development of new leads in the therapy of parasitic diseases.

/pdf/photoswitchable-assembly-of-long-lived-azobenzenes-in-water-ibtmo6og.pdf

N Lauth de Viguerie

Papers

Inhibition of the glycolytic enzymes in the trypanosome: an approach in the development of new leads in the therapy of parasitic diseases.

Photoswitchable assembly of long-lived azobenzenes in water using visible light.

Tetrafluorinated versus hydrogenated azobenzene polymers in water: access to visible-light stimulus at the expense of responsiveness