ArticleFrontiers in molecular biosciences2025
Advancing
Article in Frontiers in molecular biosciences, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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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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Authors and funding
10 authors.
Funding
Abstract
Introduction: Methods: Recombinant TcNMT was cloned, expressed, and purified for enzymatic characterization. Catalytic activity and substrate affinity were evaluated using a fluorescence-based assay. Four in-silico-selected NMT inhibitors were screened for (i) enzyme inhibition, (ii) cytotoxicity in human cardiomyocytes, and (iii) antiparasitic activity in Results: All recombinant TcNMT preparations were catalytically active and displayed high affinity for peptide substrates. Among the screened compounds, QUINE showed moderate antiparasitic efficacy but very low cytotoxicity, yielding a high selectivity index (SI = 28.11). In contrast, DDD85646 exhibited greater antiparasitic potency but substantially higher host-cell toxicity (SI = 4.67). Proteomic analysis of DDD85646-treated parasites revealed downregulation of myristoylated proteins in both life stages, including ARF GTPases and enzymes associated with vesicular trafficking and lipid metabolism. Host cell proteomes remained largely unchanged. Discussion: Biochemical characterization and phenotypic testing support TcNMT as a viable therapeutic target for Chagas disease. QUINE demonstrates the most favorable pharmacological profile, combining antiparasitic activity with excellent selectivity and low host toxicity, making it a strong lead candidate for future drug optimization. Proteomics data indicate that NMT inhibition disrupts critical pathways required for parasite viability yet spares host cellular machinery, reinforcing the mechanistic selectivity of TcNMT targeting. Further studies are warranted to improve potency and evaluate in vivo efficacy.
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