Repurposing Analysis of Nitroxoline (8-Hydroxy-5-nitroquinoline) as an Antichagasic Compound

Area of Science:

• Infectious Diseases
• Parasitology
• Drug Discovery

Background:

• Chagas disease, caused by Trypanosoma cruzi, is a neglected tropical disease with limited treatment options.
• Current drugs, benznidazole and nifurtimox, have efficacy and safety concerns.
• Drug repurposing offers a viable strategy for developing new Chagas disease therapies.

Purpose of the Study:

• To evaluate the antitrypanosomal potential of nitroxoline against Trypanosoma cruzi.
• To investigate the mechanism of parasite death induced by nitroxoline.
• To assess nitroxoline as a potential repurposed drug for Chagas disease.

Main Methods:

• Assessed nitroxoline's efficacy against epimastigote and intracellular amastigote forms of T. cruzi.
• Investigated nitroxoline's mechanism of parasite death, including apoptosis hallmarks.
• Compared nitroxoline's activity to benznidazole, a standard treatment.

Main Results:

• Nitroxoline demonstrated significantly greater efficacy than benznidazole against T. cruzi.
• Nitroxoline induced programmed cell death, characterized by chromatin condensation and mitochondrial dysfunction.
• Observed ATP depletion, ROS accumulation, and increased membrane permeability.

Conclusions:

• Nitroxoline is a potent candidate for Chagas disease repurposing, showing superior activity to benznidazole.
• The induction of programmed cell death suggests a potentially safer therapeutic profile.
• Further research into in vivo efficacy and pharmacokinetics is warranted.