Evidence map›Paper›PMID 32623208›Full record

ArticleEuropean journal of medicinal chemistry2020

Synthesis and structure activity relationships of cyanopyridone based anti-tuberculosis agents.

Yanlin Jian, Fabian Hulpia, Martijn D P Risseeuw, He Eun Forbes, Hélène Munier-Lehmann, Guy Caljon, Helena I M Boshoff, Serge Van Calenbergh

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

Article in European journal of medicinal chemistry, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
0.3field-weighted citation impact, top 32% 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

3 citing papers in PubMed, 16 citations in OpenAlex.

  1. Review
  2. Article
  3. Review
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 5 institutions in 3 countries.

Yanlin JianLaboratory for Medicinal Chemistry (FFW), Ghent University, Ottergemsesteenweg 460, B9000, Gent, Belgium.
Fabian HulpiaLaboratory for Medicinal Chemistry (FFW), Ghent University, Ottergemsesteenweg 460, B9000, Gent, Belgium.
Martijn D P RisseeuwLaboratory for Medicinal Chemistry (FFW), Ghent University, Ottergemsesteenweg 460, B9000, Gent, Belgium.
He Eun ForbesTuberculosis Research Section, Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Disease, National Institutes of Health, 9000 Rockville Pike, Bethesda, MD, 20892, United States.
Hélène Munier-LehmannUnit of Chemistry and Biocatalysis, Department of Structural Biology and Chemistry, Institut Pasteur, CNRS UMR3523, 28 Rue du Dr. Roux, Cedex 15, 75724, Paris, France.
Guy CaljonLaboratory of Microbiology, Parasitology and Hygiene, University of Antwerp, Universiteitsplein 1(S7), B2610, Wilrijk, Belgium.
Helena I M BoshoffTuberculosis Research Section, Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Disease, National Institutes of Health, 9000 Rockville Pike, Bethesda, MD, 20892, United States.
Serge Van CalenberghLaboratory for Medicinal Chemistry (FFW), Ghent University, Ottergemsesteenweg 460, B9000, Gent, Belgium. Electronic address: serge.vancalenbergh@ugent.be.
Ghent University · BEInstitut Pasteur · FRNational Institute of Allergy and Infectious Diseases · USNational Institutes of Health · USUniversity of Antwerp · BE

Funding

Development Of New Chemotherapeutics For TuberculosisZIAAI000693 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI BARRY, CLIFTON · 2009 to 2025
$20.1M
PATHOGENIC MECHANISMS OF MYCOBACTERIUM TUBERCULOSISZ01AI000693 · NIAID · NIAID EXTRAMURAL ACTIVITIES · PI BARRY, CLIFTON · 1993 to 2008
$8.1M
Intramural NIH HHS Z01 AI000693
6 · The paper itself

Abstract

Mycobacterium tuberculosis, the causative agent of tuberculosis, relies on thymidylate kinase (MtbTMPK) for the synthesis of thymidine triphosphates and thus also DNA synthesis. Therefore, this enzyme constitutes a potential Achilles heel of the pathogen. Based on a previously reported MtbTMPK 6-aryl-substituted pyridone inhibitor and guided by two co-crystal structures of MtbTMPK with pyridone- and thymine-based inhibitors, we report the synthesis of a series of aryl-shifted cyanopyridone analogues. These compounds generally lacked significant MtbTMPK inhibitory potency, but some analogues did exhibit promising antitubercular activity. Analogue 11i demonstrated a 10-fold increased antitubercular activity (MIC H37Rv, 1.2 μM) compared to literature compound 5. Many analogues with whole-cell antimycobacterial activity were devoid of significant cytotoxicity.

Indexed as

Antitubercular AgentsBacterial ProteinsCatalytic DomainDrug DesignEnzyme InhibitorsMicrobial Sensitivity TestsMolecular Docking SimulationMolecular StructureMycobacterium tuberculosisNitrilesNucleoside-Phosphate KinaseProtein BindingPyridonesStructure-Activity RelationshipAntitubercular AgentsBacterial ProteinsdTMP kinaseEnzyme InhibitorsNitrilesNucleoside-Phosphate KinasePyridonesInhibitorsThymidylate kinaseTuberculosis

Identifiers

PMID32623208
PMCPMC8362676
OpenAlexW3035094622

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.