Evidence map›Paper›PMID 36234754›Full record

ArticleMolecules (Basel, Switzerland)2022

Synthesis and Structure-Activity Relationship Studies of Pyrido [1,2-

Nicolas G Biteau, Vincent Roy, Cyril Nicolas, Hubert F Becker, Jean-Christophe Lambry, Hannu Myllykallio, Luigi A Agrofoglio

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

Article in Molecules (Basel, Switzerland), 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
0.2field-weighted citation impact, top 52% 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

0 citing papers in PubMed, 2 citations in OpenAlex.

No citing paper in PubMed yet.

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 1 country.

Nicolas G BiteauInstitute of Organic and Analytical Chemistry, CNRS UMR 7311, Université d'Orléans, Rue de Chartres, CEDEX 2, 45067 Orleans, France.ORCID 0000-0002-9625-9900
Vincent RoyInstitute of Organic and Analytical Chemistry, CNRS UMR 7311, Université d'Orléans, Rue de Chartres, CEDEX 2, 45067 Orleans, France.ORCID 0000-0002-2491-6019
Cyril NicolasInstitute of Organic and Analytical Chemistry, CNRS UMR 7311, Université d'Orléans, Rue de Chartres, CEDEX 2, 45067 Orleans, France.ORCID 0000-0002-3748-2205
Hubert F BeckerLaboratory of Optics and Biosciences, INSERM U 696-CNRS UMR 7645, Ecole Polytechnique, Route de Saclay, CEDEX, 91128 Palaiseau, France.ORCID 0000-0003-3136-6075
Jean-Christophe LambryLaboratory of Optics and Biosciences, INSERM U 696-CNRS UMR 7645, Ecole Polytechnique, Route de Saclay, CEDEX, 91128 Palaiseau, France.ORCID 0000-0001-8264-0391
Hannu MyllykallioLaboratory of Optics and Biosciences, INSERM U 696-CNRS UMR 7645, Ecole Polytechnique, Route de Saclay, CEDEX, 91128 Palaiseau, France.ORCID 0000-0002-0541-1197
Luigi A AgrofoglioInstitute of Organic and Analytical Chemistry, CNRS UMR 7311, Université d'Orléans, Rue de Chartres, CEDEX 2, 45067 Orleans, France.ORCID 0000-0002-6083-0810
Université d'Orléans · FRCentre National de la Recherche Scientifique · FR

Funding

Direction Générale de l'Armement DGA/AID and Région CVL
6 · The paper itself

Abstract

In 2002, a new class of thymidylate synthase (TS) involved in the de novo synthesis of dTMP named Flavin-Dependent Thymidylate Synthase (FDTS) encoded by the thyX gene was discovered; FDTS is present only in 30% of prokaryote pathogens and not in human pathogens, which makes it an attractive target for the development of new antibacterial agents, especially against multi-resistant pathogens. We report herein the synthesis and structure-activity relationship of a novel series of hitherto unknown pyrido[1,2-e]purine-2,4(1H,3H)-dione analogues. Several synthetics efforts were done to optimize regioselective N1-alkylation through organopalladium cross-coupling. Modelling of potential hits were performed to generate a model of interaction into the active pocket of FDTS to understand and guide further synthetic modification. All those compounds were evaluated on an in-house in vitro NADPH oxidase assays screening as well as against Mycobacterium tuberculosis ThyX. The highest inhibition was obtained for compound 23a with 84.3% at 200 µM without significant cytotoxicity (CC50 > 100 μM) on PBM cells.

Indexed as

Mycobacterium tuberculosisAnti-Bacterial AgentsDinitrocresolsFlavinsHumansNADPH OxidasesPurinesStructure-Activity RelationshipThymidine MonophosphateThymidylate Synthase4,6-dinitro-o-cresolAnti-Bacterial AgentsDinitrocresolsFlavinsNADPH OxidasesPurinesThymidine MonophosphateThymidylate Synthaseflavin-dependent thymidylate synthasepyrido[1,2-e]purine-2,4(1H,3H)-dione analoguessonogashira and Suzuki-Miyaura cross-couplingstructure-activity relationship

Identifiers

PMID36234754
PMCPMC9571937
OpenAlexW4296615124

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.