Evidence map›Paper›PMID 38780838›Full record

ArticleJournal of molecular modeling2024

Analysis of the interaction of antimalarial agents with Plasmodium falciparum glutathione reductase through molecular mechanical calculations.

Frederico Henrique do C Ferreira, L R Pinto, B A Oliveira, L V Daniel, M Navarro, G Y Sánchez Delgado

Abstract read
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In one paragraph

Article in Journal of molecular modeling, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

2 citing papers in PubMed.

  1. Review
  2. Article
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

6 authors.

Frederico Henrique do C FerreiraNEQC: Núcleo de Estudos em Química Computacional, Departament of Chemistry, Federal University of Juiz de Fora, Juiz de Fora, MG, 36.036-900, Brazil.
L R PintoNEQC: Núcleo de Estudos em Química Computacional, Departament of Chemistry, Federal University of Juiz de Fora, Juiz de Fora, MG, 36.036-900, Brazil.
B A OliveiraSINTBIOMOL: Tecnologia em Fármacos: Síntese de Biomoléculas, Avaliação Biológica e Repercussões Ambientais, Departament of Chemistry, Federal University of Juiz de Fora, Juiz de Fora, MG, 36.036-900, Brazil.
L V DanielLaQBIC: Laboratório de Química Bioinorgânica e Catálise, Departament of Chemistry, Federal University of Juiz de Fora, Juiz de Fora, MG, 36.036-900, Brazil.
M NavarroLaQBIC: Laboratório de Química Bioinorgânica e Catálise, Departament of Chemistry, Federal University of Juiz de Fora, Juiz de Fora, MG, 36.036-900, Brazil.
G Y Sánchez DelgadoLaQBIC: Laboratório de Química Bioinorgânica e Catálise, Departament of Chemistry, Federal University of Juiz de Fora, Juiz de Fora, MG, 36.036-900, Brazil. gysdelgado@ice.ufjf.br.

Funding

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior 001Fundação de Amparo à Pesquisa do Estado de Minas Gerais BPD-00777-22
6 · The paper itself

Abstract

contextMalaria remains a significant global health challenge with emerging resistance to current treatments. Plasmodium falciparum glutathione reductase (PfGR) plays a critical role in the defense mechanisms of malaria parasites against oxidative stress. In this study, we investigate the potential of targeting PfGR with conventional antimalarials and dual drugs combining aminoquinoline derivatives with GR inhibitors, which reveal promising interactions between PfGR and studied drugs. The naphthoquinone Atovaquone demonstrated particularly high affinity and potential dual-mode binding with the enzyme active site and cavity. Furthermore, dual drugs exhibit enhanced binding affinity, suggesting their efficacy in inhibiting PfGR, where the aliphatic ester bond (linker) is essential for effective binding with the enzyme's active site. Overall, this research provides important insights into the interactions between antimalarial agents and PfGR and encourages further exploration of its role in the mechanisms of action of antimalarials, including dual drugs, to enhance antiparasitic efficacy.

methodsThe drugs were tested as PfGR potential inhibitors via molecular docking on AutoDock 4, which was performed based on the preoptimized structures in HF/3-21G-PCM level of theory on ORCA 5. Drug-receptor systems with the most promising binding affinities were then studied with a molecular dynamic's simulation on AMBER 16. The molecular dynamics simulations were performed with a 100 ns NPT ensemble employing GAFF2 forcefield in the temperature of 310 K, integration time step of 2 fs, and non-bond cutoff distance of 6.0 Å.

Indexed as

AntimalarialsGlutathione ReductaseMolecular Docking SimulationMolecular Dynamics SimulationPlasmodium falciparumCatalytic DomainEnzyme InhibitorsHumansProtein BindingAntimalarialsEnzyme InhibitorsGlutathione ReductaseAntimalarialsGlutathione reductaseMalariaMolecular dockingPfGRPlasmodium falciparum

Identifiers

PMID38780838

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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 OpenQuestion graph.