Evidence map›Paper›PMID 29258359›Full record

ArticleJournal of enzyme inhibition and medicinal chemistry2018

Discovery of antimicrobial compounds targeting bacterial type FAD synthetases.

María Sebastián, Ernesto Anoz-Carbonell, Begoña Gracia, Pilar Cossio, José Antonio Aínsa, Isaías Lans, Milagros Medina

Open access · goldAbstract read
In one paragraph

Article in Journal of enzyme inhibition and medicinal chemistry, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed
2.3field-weighted citation impact, top 12% of its field
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

15 citing papers in PubMed, 30 citations in OpenAlex.

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  12. Frontiers in genetics · 2020
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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

7 authors at 2 institutions in 3 countries.

María Sebastiána Departamento de Bioquímica y Biología Molecular y Celular, Facultad de Ciencias , Universidad de Zaragoza , Zaragoza , Spain.ORCID http://orcid.org/0000-0002-5593-8624
Ernesto Anoz-Carbonella Departamento de Bioquímica y Biología Molecular y Celular, Facultad de Ciencias , Universidad de Zaragoza , Zaragoza , Spain.
Begoña Graciac Grupo de Genética de Micobacterias, Departamento de Microbiología, Medicina Preventiva y Salud Pública. Facultad de Medicina , Universidad de Zaragoza , Zaragoza , Spain.
Pilar Cossioe Department of Theoretical Biophysics , Max Planck Institute of Biophysics , Frankfurt , Germany.
José Antonio Aínsab Institute of Biocomputation and Physics of Complex Systems (BIFI-IQFR and CBsC-CSIC Joint Units) , Universidad de Zaragoza , Zaragoza , Spain.ORCID http://orcid.org/0000-0003-2076-844X
Isaías Lansf Biophysics of Tropical Diseases, Max Planck Tandem Group , University of Antioquia , Medellín , Colombia.
Milagros Medinaa Departamento de Bioquímica y Biología Molecular y Celular, Facultad de Ciencias , Universidad de Zaragoza , Zaragoza , Spain.ORCID http://orcid.org/0000-0001-8743-0182
Universidad de Zaragoza · ESUniversidad de Antioquia · CO

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The increase of bacterial strains resistant to most of the available antibiotics shows a need to explore novel antibacterial targets to discover antimicrobial drugs. Bifunctional bacterial FAD synthetases (FADSs) synthesise the flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD). These cofactors act in vital processes as part of flavoproteins, making FADS an essential enzyme. Bacterial FADSs are potential antibacterial targets because of differences to mammalian enzymes, particularly at the FAD producing site. We have optimised an activity-based high throughput screening assay targeting Corynebacterium ammoniagenes FADS (CaFADS) that identifies inhibitors of its different activities. We selected the three best high-performing inhibitors of the FMN:adenylyltransferase activity (FMNAT) and studied their inhibition mechanisms and binding properties. The specificity of the CaFADS hits was evaluated by studying also their effect on the Streptococcus pneumoniae FADS activities, envisaging differences that can be used to discover species-specific antibacterial drugs. The antimicrobial effect of these compounds was also evaluated on C. ammoniagenes, S. pneumoniae, and Mycobacterium tuberculosis cultures, finding hits with favourable antimicrobial properties.

Indexed as

Drug DiscoveryAnti-Bacterial AgentsCorynebacteriumDose-Response Relationship, DrugEnzyme InhibitorsMicrobial Sensitivity TestsMolecular Docking SimulationMolecular StructureMycobacterium tuberculosisNucleotidyltransferasesStreptococcus pneumoniaeStructure-Activity RelationshipAnti-Bacterial AgentsEnzyme InhibitorsFMN adenylyltransferaseNucleotidyltransferasesBacterial FAD Synthetasedrug discoveryhigh-throughput screeningStreptococcus pneumoniae

Identifiers

PMID29258359
PMCPMC7012052
OpenAlexW2779079843

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.