Eprinomectin Inhibits Leishmania by Inducing Mitochondrial Dysfunction and Cell Cycle Arrest

Area of Science:

• Parasitology
• Drug Discovery
• Molecular Biology

Background:

• Leishmaniasis is a major global health concern with limited treatment options due to toxicity, resistance, and cost.
• Current therapies for leishmaniasis face significant challenges, necessitating novel therapeutic strategies.

Purpose of the Study:

• To evaluate the antileishmanial efficacy of eprinomectin, a veterinary macrocyclic lactone.
• To elucidate the mechanisms of action of eprinomectin against Leishmania parasites.
• To explore eprinomectin's potential as a foundation for new antileishmanial drug development.

Main Methods:

• Assessed antileishmanial activity using in vitro and in vivo models.
• Employed scanning electron microscopy (SEM) for morphological analysis.
• Conducted transcriptomic profiling, reactive oxygen species (ROS) measurements, and in vivo parasite burden assessment.

Main Results:

• Eprinomectin demonstrated selective activity against Leishmania, causing morphological abnormalities indicative of antiproliferative effects.
• In vivo treatment significantly reduced parasite load and antigen levels.
• Transcriptomic data revealed mitochondrial dysfunction, increased ROS, metabolic stress, and S-phase cell cycle arrest.

Conclusions:

• Eprinomectin exhibits multimodal antileishmanial effects via direct parasiticidal mechanisms.
• The drug's efficacy in reducing parasite burden and disrupting key cellular processes supports its potential for drug development.
• Further investigation into eprinomectin's translational potential, including combination therapies, is recommended.