Evidence map›Paper›PMID 38784473›Full record

ArticleRSC medicinal chemistry2024

Evaluation of ketoclomazone and its analogues as inhibitors of 1-deoxy-d-xylulose 5-phosphate synthases and other thiamine diphosphate (ThDP)-dependent enzymes.

Alex H Y Chan, Terence C S Ho, Imam Fathoni, Rawia Hamid, Anna K H Hirsch, Kevin J Saliba, Finian J Leeper

Abstract read
In one paragraph

Article in RSC medicinal chemistry, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing 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

4 citing papers in PubMed.

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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.

Alex H Y ChanYusuf Hamied Department of Chemistry, University of Cambridge Lensfield Road Cambridge CB2 1EW UK fjl1@cam.ac.uk.ORCID https://orcid.org/0009-0006-7897-4560
Terence C S HoYusuf Hamied Department of Chemistry, University of Cambridge Lensfield Road Cambridge CB2 1EW UK fjl1@cam.ac.uk.
Imam FathoniResearch School of Biology, The Australian National University Canberra ACT 2601 Australia.
Rawia HamidHelmholtz Institute for Pharmaceutical Research Saarland (HIPS) - Helmholtz Centre for Infection Research (HZI) Campus Building E8.1 66123 Saarbrücken Germany.ORCID https://orcid.org/0000-0001-9211-6286
Anna K H HirschHelmholtz Institute for Pharmaceutical Research Saarland (HIPS) - Helmholtz Centre for Infection Research (HZI) Campus Building E8.1 66123 Saarbrücken Germany.
Kevin J SalibaResearch School of Biology, The Australian National University Canberra ACT 2601 Australia.ORCID https://orcid.org/0000-0003-3345-8440
Finian J LeeperYusuf Hamied Department of Chemistry, University of Cambridge Lensfield Road Cambridge CB2 1EW UK fjl1@cam.ac.uk.ORCID https://orcid.org/0000-0003-3408-5199

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Most pathogenic bacteria, apicomplexan parasites and plants rely on the methylerythritol phosphate (MEP) pathway to obtain precursors of isoprenoids. 1-Deoxy-d-xylulose 5-phosphate synthase (DXPS), a thiamine diphosphate (ThDP)-dependent enzyme, catalyses the first and rate-limiting step of the MEP pathway. Due to its absence in humans, DXPS is considered as an attractive target for the development of anti-infectious agents and herbicides. Ketoclomazone is one of the earliest reported inhibitors of DXPS and antibacterial and herbicidal activities have been documented. This study investigated the activity of ketoclomazone on DXPS from various species, as well as the broader ThDP-dependent enzyme family. To gain further insights into the inhibition, we have prepared analogues of ketoclomazone and evaluated their activity in biochemical and computational studies. Our findings support the potential of ketoclomazone as a selective antibacterial agent.

Identifiers

PMID38784473
PMCPMC11110791

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Registered trials

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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.