Evidence map›Paper›PMID 41567861›Full record

ArticleFrontiers in molecular biosciences2025

Advancing

Diana González García, Angel Torres, Alan Talevi, Lucas N Alberca, Miguel A Beltran, Frida Lara, Marina Da Silva Ferreira, Priscila S G Farani, Igor C Almeida, Rosa A Maldonado

Abstract read
In one paragraph

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.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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.

2 · The registry

The trial behind it

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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors.

Diana González GarcíaDepartment of Biological Sciences, The University of Texas at El Paso, El Paso, TX, United States.
Angel TorresDepartment of Biological Sciences, The University of Texas at El Paso, El Paso, TX, United States.
Alan TaleviLaboratory of Bioactive Compounds Research and Development (LIDeB), Faculty of Exact Sciences, National University of La Plata (UNLP), La Plata, Buenos Aires, Argentina.
Lucas N AlbercaLaboratory of Bioactive Compounds Research and Development (LIDeB), Faculty of Exact Sciences, National University of La Plata (UNLP), La Plata, Buenos Aires, Argentina.
Miguel A BeltranDepartment of Biological Sciences, The University of Texas at El Paso, El Paso, TX, United States.
Frida LaraDepartment of Biological Sciences, The University of Texas at El Paso, El Paso, TX, United States.
Marina Da Silva FerreiraDepartment of Biological Sciences, The University of Texas at El Paso, El Paso, TX, United States.
Priscila S G FaraniDepartment of Biological Sciences, The University of Texas at El Paso, El Paso, TX, United States.
Igor C AlmeidaDepartment of Biological Sciences, The University of Texas at El Paso, El Paso, TX, United States.
Rosa A MaldonadoDepartment of Biological Sciences, The University of Texas at El Paso, El Paso, TX, United States.

Funding

UTEP Border Biomedical Research CenterU54MD007592 · NIMHD · UNIVERSITY OF TEXAS EL PASO · PI Gabriel Andrew Frietze · 2019 to 2026
$35.1M
TOXICOLOGY PROJECTG12RR008124 · NCRR · UNIVERSITY OF TEXAS EL PASO · PI AGUILERA, RENATO J · 1992 to 2011
$20.8M
TCCG12MD007592 · NIMHD · UNIVERSITY OF TEXAS EL PASO · PI KIRKEN, ROBERT A. · 2012 to 2018
$19.4M
New Treatments for Chronic Chagas DiseaseSC1GM139714 · NIGMS · UNIVERSITY OF TEXAS EL PASO · PI MALDONADO, ROSA A · 2021 to 2024
$1.5M
NCRR NIH HHS G12 RR008124NIGMS NIH HHS SC1 GM139714NIMHD NIH HHS G12 MD007592NIMHD NIH HHS U54 MD007592
6 · The paper itself

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.

Indexed as

Chagas diseasedrug targetsinhibitionN-myristoyl-transferaseTrypanosoma cruzi

Identifiers

PMID41567861
PMCPMC12816245

What OpenQuestion holds

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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.