Evidence map›Paper›PMID 21705805›Full record

ArticleThe Journal of biological chemistry2011

PG12, a phospholipid analog with potent antimalarial activity, inhibits Plasmodium falciparum CTP:phosphocholine cytidylyltransferase activity.

Patricia González-Bulnes, April M Bobenchik, Yoann Augagneur, Rachel Cerdan, Henri J Vial, Amadeu Llebaria, Choukri Ben Mamoun

Open access · hybridAbstract read
In one paragraph

Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
0.6field-weighted citation impact, top 33% 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

10 citing papers in PubMed, 25 citations in OpenAlex.

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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 at 4 institutions in 3 countries.

Patricia González-BulnesResearch Unit on BioActive Molecules (RUBAM), Departament de Química Biomèdica, Instituto de Química Avanzada de Cataluña IQAC, CSIC, Jordi Girona 18-26, 08034 Barcelona, Spain.
April M BobenchikDepartment of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut 06520, and.
Yoann AugagneurDepartment of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut 06520, and.
Rachel CerdanDynamique des Interactions Membranaires Normales et Pathologiques, CNRS UMR 5235, Universite Montpellier II, 34095 Montpellier, France.
Henri J VialDynamique des Interactions Membranaires Normales et Pathologiques, CNRS UMR 5235, Universite Montpellier II, 34095 Montpellier, France.
Amadeu LlebariaResearch Unit on BioActive Molecules (RUBAM), Departament de Química Biomèdica, Instituto de Química Avanzada de Cataluña IQAC, CSIC, Jordi Girona 18-26, 08034 Barcelona, Spain,. Electronic address: alsqob@cid.csic.es.
Choukri Ben MamounDepartment of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut 06520, and. Electronic address: Choukri.benmamoun@yale.edu.
Yale University · USInstituto de Química Orgánica General · ESCentre National de la Recherche Scientifique · FRLaboratory of Pathogens and Host Immunity · FR

Funding

Nucleoside Transporters of Plasmodium falciparumR01AI051507 · NIAID · OREGON HEALTH & SCIENCE UNIVERSITY · PI ULLMAN, BUDDY · 2003 to 2007
$1.7M
NIAID NIH HHS AI51507NIAID NIH HHS R01 AI051507
6 · The paper itself

Abstract

In the human malaria parasite Plasmodium falciparum, the synthesis of the major and essential membrane phospholipid, phosphatidylcholine, occurs via the CDP-choline and the serine decarboxylase phosphoethanolamine methylation (SDPM) pathways, which are fueled by host choline, serine, and fatty acids. Both pathways share the final two steps catalyzed by two essential enzymes, P. falciparum CTP:phosphocholine cytidylyltransferase (PfCCT) and choline-phosphate transferase (PfCEPT). We identified a novel class of phospholipid mimetics, which inhibit the growth of P. falciparum as well as Leishmania and Trypanosoma species. Metabolic analyses showed that one of these compounds, PG12, specifically blocks phosphatidylcholine biosynthesis from both the CDP-choline and SDPM pathways via inhibition of PfCCT. In vitro studies using recombinant PfCCT showed a dose-dependent inhibition of the enzyme by PG12. The potent antimalarial of this compound, its low cytotoxicity profile, and its established mode of action make it an excellent lead to advance for further drug development and efficacy in vivo.

Indexed as

AntimalarialsBiomimetic MaterialsCholine-Phosphate CytidylyltransferaseDose-Response Relationship, DrugEnzyme InhibitorsHumansMalaria, FalciparumPhospholipidsPlasmodium falciparumProtozoan ProteinsAntimalarialsCholine-Phosphate CytidylyltransferaseEnzyme InhibitorsPhospholipidsProtozoan Proteins

Identifiers

PMID21705805
PMCPMC3190701
OpenAlexW1970438062

What OpenQuestion holds

Textmetadata
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.