Evidence map›Paper›PMID 25656411›Full record

ArticleThe Journal of antimicrobial chemotherapy2015

Tetrahydroisoquinolines affect the whole-cell phenotype of Mycobacterium tuberculosis by inhibiting the ATP-dependent MurE ligase.

Juan D Guzman, Thomas Pesnot, Diana A Barrera, Heledd M Davies, Eleanor McMahon, Dimitrios Evangelopoulos, Parisa N Mortazavi, Tulika Munshi, Arundhati Maitra, Eleanor D Lamming and 8 more

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

Article in The Journal of antimicrobial chemotherapy, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed
0.5field-weighted citation impact, top 35% 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

14 citing papers in PubMed, 31 citations in OpenAlex.

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  11. The Pictet-Spengler Reaction Updates Its Habits.Molecules (Basel, Switzerland) · 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

18 authors at 4 institutions in 2 countries.

Juan D GuzmanMycobacteria Research Laboratory, Institute of Structural and Molecular Biology, Department of Biological Sciences, Birkbeck, University of London, Malet Street, London WC1E 7HX, UK.
Thomas PesnotDepartment of Chemistry, University College London, 20 Gordon Street, London WC1H 0AJ, UK.
Diana A BarreraDepartamento de Química, Facultad de Ciencias, Universidad Nacional de Colombia, Carrera 30 No. 45-03, Bogotá, Colombia.
Heledd M DaviesMycobacteria Research Laboratory, Institute of Structural and Molecular Biology, Department of Biological Sciences, Birkbeck, University of London, Malet Street, London WC1E 7HX, UK.
Eleanor McMahonMycobacteria Research Laboratory, Institute of Structural and Molecular Biology, Department of Biological Sciences, Birkbeck, University of London, Malet Street, London WC1E 7HX, UK.
Dimitrios EvangelopoulosMycobacteria Research Laboratory, Institute of Structural and Molecular Biology, Department of Biological Sciences, Birkbeck, University of London, Malet Street, London WC1E 7HX, UK.
Parisa N MortazaviMycobacteria Research Laboratory, Institute of Structural and Molecular Biology, Department of Biological Sciences, Birkbeck, University of London, Malet Street, London WC1E 7HX, UK.
Tulika MunshiMycobacteria Research Laboratory, Institute of Structural and Molecular Biology, Department of Biological Sciences, Birkbeck, University of London, Malet Street, London WC1E 7HX, UK.
Arundhati MaitraMycobacteria Research Laboratory, Institute of Structural and Molecular Biology, Department of Biological Sciences, Birkbeck, University of London, Malet Street, London WC1E 7HX, UK.
Eleanor D LammingDepartment of Chemistry, University College London, 20 Gordon Street, London WC1H 0AJ, UK.
Richard AngellDrug Discovery Group, UCL School of Pharmacy, 29-39 Brunswick Square, London WC1N 1AX, UK.
Markus C GershaterThe Advanced Centre for Biochemical Engineering, University College London, Gordon Street, London WC1H 0AH, UK.
Joanna M RedmondDepartment of Medicinal Chemistry, GlaxoSmithKline Medicines Research Centre, Gunnels Wood Road, Stevenage, Hertfordshire SG1 2NY, UK.
Deborah NeedhamDepartment of Medicinal Chemistry, GlaxoSmithKline Medicines Research Centre, Gunnels Wood Road, Stevenage, Hertfordshire SG1 2NY, UK.
John M WardDrug Discovery Group, UCL School of Pharmacy, 29-39 Brunswick Square, London WC1N 1AX, UK.
Luis E CucaDepartamento de Química, Facultad de Ciencias, Universidad Nacional de Colombia, Carrera 30 No. 45-03, Bogotá, Colombia.
Helen C HailesDepartment of Chemistry, University College London, 20 Gordon Street, London WC1H 0AJ, UK.
Sanjib BhaktaMycobacteria Research Laboratory, Institute of Structural and Molecular Biology, Department of Biological Sciences, Birkbeck, University of London, Malet Street, London WC1E 7HX, UK s.bhakta@bbk.ac.uk sanjib.bhakta@ucl.ac.uk.
Institute of Structural and Molecular Biology · GBUniversity College London · GBGlaxoSmithKline (United Kingdom) · GBUniversidad Nacional de Colombia · CO

Funding

Biotechnology and Biological Sciences Research Council BB/G014426/1Medical Research Council G0801956
6 · The paper itself

Abstract

objectives(S)-Leucoxine, isolated from the Colombian Lauraceae tree Rhodostemonodaphne crenaticupula Madriñan, was found to inhibit the growth of Mycobacterium tuberculosis H37Rv. A biomimetic approach for the chemical synthesis of a wide array of 1-substituted tetrahydroisoquinolines was undertaken with the aim of elucidating a common pharmacophore for these compounds with novel mode(s) of anti-TB action.

methodsBiomimetic Pictet-Spengler or Bischler-Napieralski synthetic routes were employed followed by an evaluation of the biological activity of the synthesized compounds.

resultsIn this work, the synthesized tetrahydroisoquinolines were found to inhibit the growth of M. tuberculosis H37Rv and affect its whole-cell phenotype as well as the activity of the ATP-dependent MurE ligase, a key enzyme involved in the early stage of cell wall peptidoglycan biosynthesis.

conclusionsAs the correlation between the MIC and the half-inhibitory enzymatic concentration was not particularly strong, there is a credible possibility that these compounds have pleiotropic mechanism(s) of action in M. tuberculosis.

Indexed as

Antitubercular AgentsBacterial ProteinsEnzyme InhibitorsMicrobial Sensitivity TestsMycobacterium tuberculosisPeptide SynthasesTetrahydroisoquinolinesAntitubercular AgentsBacterial ProteinsEnzyme InhibitorsMurE protein, Mycobacterium tuberculosisPeptide SynthasesTetrahydroisoquinolinesaporphine alkaloidscell wall peptidoglycandrug resistanceMycobacterium tuberculosisSPOTiTBtuberculosis

Identifiers

PMID25656411
PMCPMC4498294
OpenAlexW2138686621

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.