ArticleJournal of medicinal chemistry2025
Dissecting Structural Requirements of Leucinostatin A Derivatives for Antiprotozoal Activity and Mammalian Toxicity.
Article in Journal of medicinal chemistry, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
3 citing papers in PubMed.
- Article
- A trypanosome-specific complex mediates late-stage processing of cytosolic LSU rRNA.Nucleic acids research · 2025Article
- Targeting the Mitochondria in High-Grade Gliomas.Cancers · 2025Review
Corrections and comments
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Authors and funding
10 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Lefleuganan, a clinical stage drug candidate for the treatment of cutaneous leishmaniasis, is a synthetic nonapeptide inspired by the natural antimicrobial peptide leucinostatin A, exhibiting excellent antiprotozoal activity in the low nM range. Lefleuganan shows strongly reduced acute toxicity, making it amenable for clinical use. Here, using a broad set of in vivo and in vitro measurements using purified enzymes, we find that leucinostatin A, but not lefleuganan, specifically targets the mitochondrial ATP synthase, inhibiting ATP synthesis by the human, bovine, and yeast enzyme in the nanomolar range. In a structure-activity relationship study covering the chemical space between the two compounds, hydroxyleucine at position 7 in leucinostatin A is identified as the key responsible moiety for specific ATP synthase inhibition and systemic toxicity. Our data suggest that efficient antiprotozoal activity of these class of compounds is mediated by efficient energetic uncoupling of negatively charged membranes.
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Registered trials
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