Evidence map›Paper›PMID 31454170›Full record

ArticleChemMedChem2019

Integrated Target-Based and Phenotypic Screening Approaches for the Identification of Anti-Tubercular Agents That Bind to the Mycobacterial Adenylating Enzyme MbtA.

Lindsay Ferguson, Geoff Wells, Sanjib Bhakta, James Johnson, Junitta Guzman, Tanya Parish, Robin A Prentice, Federico Brucoli

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in ChemMedChem, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
0.7field-weighted citation impact, top 30% 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

5 citing papers in PubMed, 11 citations in OpenAlex.

  1. Article
  2. TargetingRSC medicinal chemistry · 2023
    Review
  3. Review
  4. Article
  5. Hit Compounds and Associated Targets in IntracellularMolecules (Basel, Switzerland) · 2022
    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

8 authors at 6 institutions in 2 countries.

Lindsay FergusonSchool of Science, University of the West of Scotland, Paisley, PA1 2BE, UK.
Geoff WellsUCL School of Pharmacy, University College London, 29/39 Brunswick Square, London, WC1N 1AX, UK.
Sanjib BhaktaDepartment of Biological Sciences, Institute of Structural and Molecular Biology, Birkbeck, University of London, London, WC1E 7HX, UK.
James JohnsonTB Discovery Research, Infectious Disease Research Institute, 1616 Eastlake Avenue East, Seattle, WA, 98102, USA.
Junitta GuzmanTB Discovery Research, Infectious Disease Research Institute, 1616 Eastlake Avenue East, Seattle, WA, 98102, USA.
Tanya ParishTB Discovery Research, Infectious Disease Research Institute, 1616 Eastlake Avenue East, Seattle, WA, 98102, USA.
Robin A PrenticeSeattle Structural Genomics Center for Infectious Disease, Seattle, WA, USA.
Federico BrucoliLeicester School of Pharmacy, De Montfort University, Leicester, LE1 9BH, UK.ORCID 0000-0001-8661-2910
Infectious Disease Research Institute · USCenter for Infectious Disease Research · USDe Montfort University · GBInstitute of Structural and Molecular Biology · GBUniversity College London · GBUniversity of the West of Scotland · GB

Funding

Medical Research Council G0802079NIAID NIH HHS HHSN272200700057CNIAID NIH HHS HHSN272201200025CNIAID NIH HHS HHSN272201700059C
6 · The paper itself

Abstract

Iron is essential for the pathogenicity and virulence of Mycobacterium tuberculosis, which synthesises salicyl-capped siderophores (mycobactins) to acquire this element from the host. MbtA is the adenylating enzyme that catalyses the initial reaction of mycobactin biosynthesis and is solely expressed by mycobacteria. A 3200-member library comprised of lead-like, structurally diverse compounds was screened against M. tuberculosis for whole-cell inhibitory activity. A set of 846 compounds that inhibited the tubercle bacilli growth were then tested for their ability to bind to MbtA using a fluorescence-based thermal shift assay and NMR-based Water-LOGSY and saturation transfer difference (STD) experiments. We identified an attractive hit molecule, 5-hydroxyindol-3-ethylamino-(2-nitro-4-trifluoromethyl)benzene (5), that bound with high affinity to MbtA and produced a MIC

Indexed as

AdenosineAntitubercular AgentsCatalytic DomainCell SurvivalHep G2 CellsHumansIronLigandsLigasesMicrobial Sensitivity TestsMolecular Docking SimulationMolecular StructureMycobacterium tuberculosisOxazolesSiderophoresSmall Molecule LibrariesAdenosineAntitubercular AgentsIronLigandsLigasesmycobactinsOxazolessalicyl-AMP ligase, Mycobacterium tuberculosisSiderophoresSmall Molecule Librariescompound screeningiron homeostasismycobactinsNMR spectroscopysiderophorestuberculosis

Identifiers

PMID31454170
PMCPMC6800809
OpenAlexW2970248842

What OpenQuestion holds

Textmetadata
LicenceTDM
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.