Evidence map›Paper›PMID 41844697›Full record

ArticleScientific reports2026

In silico discovery of thioglycoside analogues as donor-site inhibitors of glycosyltransferase LgtC.

Olimpo Sierra-Hernández, Oscar Saurith-Coronell, Jackson J Alcázar, Eliceo Cortés, Maryury C Flores-Sumoza, Juan D Rodríguez-Macías, José R Mora, Yovani Marrero-Ponce, Ernesto Contreras-Torres, Edgar A Márquez Brazón

Abstract read
In one paragraph

Article in Scientific reports, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. Frontiers in bioinformatics · 2026
    Review
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.

Olimpo Sierra-Hernández *Departamento de Medicina, División Ciencias de la Salud, Universidad del Norte, Km 5, Vía Puerto Colombia, Puerto Colombia, 081007, Colombia. olimpos@uninorte.edu.co.
Oscar Saurith-CoronellDepartamento de Medicina, División Ciencias de la Salud, Universidad del Norte, Km 5, Vía Puerto Colombia, Puerto Colombia, 081007, Colombia.
Jackson J AlcázarCentro de Química Médica, Instituto de Ciencias e Innovación en Medicina, Facultad de Medicina, Clínica Alemana Universidad del Desarrollo, Santiago, Chile.
Eliceo CortésGrupo de Investigación en Sociedad, Educación y Desarrollo HumanoGISEDH, Facultad de Ciencias, Educación, Artes y Humanidades, Institución Universitaria de Barranquilla, Barranquilla, 080002, Colombia.
Maryury C Flores-SumozaPrograma de Química y Farmacia, Facultad de Ciencias Básicas y Biomédicas, Universidad Simón Bolívar, Carrera 59 N° 59-65, Barranquilla, 080002, Colombia.
Juan D Rodríguez-MacíasFacultad de Ciencias de la Salud, Exactas y Naturales, Universidad Libre, Barranquilla, 080001, Colombia.
José R MoraGrupo de Química Computacional y Teórica (QCT-USFQ), Departamento de Ingeniería Química, Universidad San Fr Facultad de Ingeniería, Universidad Panamericana, Augusto Rodin No. 498, Insurgentes Mixcoac, Benito Juárez, Ciudad de México, 03920, Mexico.
Yovani Marrero-PonceUniversidad Panamericana, Augusto Rodin No. 498, Insurgentes Mixcoac, Benito Juárez, Ciudad de México, 03920, Mexico.
Ernesto Contreras-TorresUniversidad Panamericana, Augusto Rodin No. 498, Insurgentes Mixcoac, Benito Juárez, Ciudad de México, 03920, Mexico.
Edgar A Márquez Brazón *Grupo de Investigaciones en Química y Biología, Departamento de Química y Biología, Facultad de Ciencias Básicas, Universidad del Norte, Carrera 51B, Km 5, Vía Puerto Colombia, Barranquilla, 081007, Colombia. ebrazon@uninorte.edu.co.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The growing prevalence of multidrug-resistant Gram-negative pathogens highlights the urgent need for therapeutic strategies that complement traditional antibiotics by targeting essential virulence pathways. Glycosyltransferase LgtC, a key enzyme in lipooligosaccharide (LOS) biosynthesis, represents an attractive target for antivirulence approaches because of its essential role in bacterial immune evasion and pathogenicity. In this work, we employed an integrated in silico pipeline to identify thioglycoside analogs structurally related to the metabolic decoys FucSBn and BacSBn, evaluating their potential to hit the UDP-galactose donor pocket of LgtC. A similarity-based screening in PubChem, followed by ADME-Tox filtering yield 18 candidate analogs. Molecular docking using AutoDock-GPU revealed several candidates, most notably C-5 (- 8.36 kcal/mol) and C-18 (- 8.13 kcal/mol), to bind favorably within the donor site, showing more negative mean scoring values than natural donor UDP-α-D-galactose (- 6.74 kcal/mol). Redocking of the natural ligand reproduced the crystallographic pose, supporting the reliability of the docking protocol. To assess dynamic behavior, 100 ns molecular dynamics simulations (AMBER14) were performed for each complex. The top-scoring analogs maintained stable binding poses, with RMSD values of ~ 2.0-3.0 Å and preserved donor-like hydrogen-bond networks complemented by π-stacking and sulfur-mediated contacts. These interaction patterns suggest that the thioglycoside analogs may occupy the donor site in a manner compatible with competitive binding. While docking and MD describe different aspects of ligand recognition, several trends observed in docking, such as the favorable binding scores of C-5 and C-18, are broadly consistent with their ability to maintain stable poses during MD. Based on this consistency and scoring, the thioglycoside scaffolds C-5, C-14, and C-18 emerge as computationally prioritized candidates for subsequent biochemical testing against LgtC. Furthermore, these scaffolds offer a mechanistic basis and putative starting points for future structure-based optimization of thioglycoside analogs aimed at disrupting LOS biosynthesis in multidrug-resistant Gram-negative bacteria.

Indexed as

Bacterial ProteinsEnzyme InhibitorsGlycosyltransferasesThioglycosidesBinding SitesComputer SimulationDrug DiscoveryMolecular Docking SimulationMolecular Dynamics SimulationProtein BindingBacterial ProteinsEnzyme InhibitorsGlycosyltransferasesThioglycosidesAntivirulence strategyGlycosyltransferase LgtC inhibitionGram-negative bacteriaIn silico drug discoveryThioglycoside analogues

Identifiers

PMID41844697
PMCPMC13128908

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
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Registered trials

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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 Socratic graph.