Evidence map›Paper›PMID 41697521›Full record

ArticleFolia microbiologica2026

Evaluation of the effects of hybrids of metronidazole and eugenol analogues as inhibitors of the Staphylococcus aureus NorA efflux pump: an in vitro and in silico analysis.

Lucas Dos Santos Sa, João Arthur de Oliveira Borges, Francisco Ruan Moreira da Silva Santos, Cicera Laura Roque Paulo, Daniel Sampaio Alves, Ewerton Yago de Sousa Rodrigues, Ray Silva de Almeida, Sheila Alves Gonçalves, Cícera Datiane de Morais Oliveira Tintino, Lucas Lopardi Franco and 7 more

Abstract read
PubMed Publisher
In one paragraph

Article in Folia microbiologica, 2026. 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

17 authors.

Lucas Dos Santos SaDepartamento de Química Biológica, Laboratório de Microbiologia e Biologia Molecular - LMBM, Universidade Regional do Cariri, Crato, Ceará, Brasil.
João Arthur de Oliveira BorgesDepartamento de Química Biológica, Laboratório de Microbiologia e Biologia Molecular - LMBM, Universidade Regional do Cariri, Crato, Ceará, Brasil.
Francisco Ruan Moreira da Silva SantosDepartamento de Física, Universidade Regional do Cariri, Juazeiro do Norte, CE, Brasil.
Cicera Laura Roque PauloDepartamento de Química Biológica, Laboratório de Microbiologia e Biologia Molecular - LMBM, Universidade Regional do Cariri, Crato, Ceará, Brasil.
Daniel Sampaio AlvesDepartamento de Química Biológica, Laboratório de Microbiologia e Biologia Molecular - LMBM, Universidade Regional do Cariri, Crato, Ceará, Brasil.
Ewerton Yago de Sousa RodriguesDepartamento de Química Biológica, Laboratório de Microbiologia e Biologia Molecular - LMBM, Universidade Regional do Cariri, Crato, Ceará, Brasil.
Ray Silva de AlmeidaDepartamento de Química Biológica, Laboratório de Microbiologia e Biologia Molecular - LMBM, Universidade Regional do Cariri, Crato, Ceará, Brasil.
Sheila Alves GonçalvesDepartamento de Química Biológica, Laboratório de Microbiologia e Biologia Molecular - LMBM, Universidade Regional do Cariri, Crato, Ceará, Brasil.
Cícera Datiane de Morais Oliveira TintinoDepartamento de Química Biológica, Laboratório de Microbiologia e Biologia Molecular - LMBM, Universidade Regional do Cariri, Crato, Ceará, Brasil.
Lucas Lopardi FrancoFaculdade de Ciências Farmacêuticas, Universidade Federal de Alfenas, Alfenas, MG, 37130-001, Brazil.
Ana Laura Marques TrincaFaculdade de Ciências Farmacêuticas, Universidade Federal de Alfenas, Alfenas, MG, 37130-001, Brazil.
Douglas Henriques NovaisFaculdade de Ciências Farmacêuticas, Universidade Federal de Alfenas, Alfenas, MG, 37130-001, Brazil.
Francisco Nascimento PereiraCentro de Ciências Agrárias e da Biodiversidade - CCAB, Universidade Federal Do Cariri, Crato, CE, Brasil.
Maria Karollyna Nascimento do Silva LeandroDepartamento de Química Biológica, Laboratório de Microbiologia e Biologia Molecular - LMBM, Universidade Regional do Cariri, Crato, Ceará, Brasil.
José Bezerra de Araújo-NetoPrograma de Pós-Graduação em Ciências Biológicas, Centro de Biociências, Universidade Federal de Pernambuco, Recife, 50670-901, PE, Brasil.
Henrique Douglas Melo CoutinhoDepartamento de Química Biológica, Laboratório de Microbiologia e Biologia Molecular - LMBM, Universidade Regional do Cariri, Crato, Ceará, Brasil. hdmcoutinho@gmail.com.ORCID http://orcid.org/0000-0002-6634-4207
Janaina Esmeraldo RochaDepartamento de Química Biológica, Laboratório de Microbiologia e Biologia Molecular - LMBM, Universidade Regional do Cariri, Crato, Ceará, Brasil.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Staphylococcus aureus is a Gram-positive coccus-type bacterium responsible for colonizing various sites of the host’s body, thus generating several pathologies such as pneumonia, osteomyelitis, endocarditis, and even cases of sepsis. Eugenol, dihydroeugenol, guaiacol, and phenol are phenolic compounds with antimicrobial activities, as is the drug metronidazole; therefore, eight substances were synthesized by coupling metronidazole with the molecules mentioned above, thus originating the compounds AD1–AD8. The present study aimed to evaluate the antibacterial activity and the capacity of the compounds AD1–AD8 to amplify the action of norfloxacin and ethidium bromide against the S. aureus 1199B strain through the inhibition of the NorA efflux pump. Broth microdilution assays were performed to determine the MIC and to analyze the association of the compounds AD1–AD8 with norfloxacin and ethidium bromide, along with the membrane permeability test and molecular docking. The compounds AD1–AD8 obtained positive results as they exhibited a potentiating effect by reducing the MIC of norfloxacin and ethidium bromide against 1199B, thus evidencing interference with the functioning of the NorA efflux pump, which had already been predicted by the data obtained from the molecular docking assay, in addition to having demonstrated significant effects by acting on the S. aureus membrane. The information obtained from this research is in line with what is reported in the literature regarding the effects observed with eugenol, dihydroeugenol, and guaiacol and their derivatives when combined with other antibiotics against S. aureus strains that possess efflux pumps, with competitive inhibition being observed, as well as the possibility that the reduction in MIC may have occurred due to a reduction in gene expression levels. Further assays are needed to evaluate these possibilities. Based on the presented data, it was found that the compounds AD1–AD8 exhibit promising aspects to act as antibiotic adjuvants.

Indexed as

Bacterial resistanceDihydroeugenolEfflux pumpEugenolGuaiacolMetronidazolePhenolStaphylococcus aureus

Identifiers

What OpenQuestion holds

Textmetadata
Read underepoch 390

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.