Evidence map›Paper›PMID 38719808›Full record

ArticleNature communications2024

Identification of a family of species-selective complex I inhibitors as potential anthelmintics.

Taylor Davie, Xènia Serrat, Lea Imhof, Jamie Snider, Igor Štagljar, Jennifer Keiser, Hiroyuki Hirano, Nobumoto Watanabe, Hiroyuki Osada, Andrew G Fraser

Abstract read
In one paragraph

Article in Nature communications, 2024. 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
–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

3 citing papers in PubMed.

  1. Article
  2. Review
  3. Article
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

10 authors.

Taylor DavieThe Donnelly Centre, University of Toronto, 160 College Street, Toronto, M5S 3E1, Canada.
Xènia SerratThe Donnelly Centre, University of Toronto, 160 College Street, Toronto, M5S 3E1, Canada.
Lea ImhofSwiss Tropical and Public Health Institute, Kreuzstrasse 2, CH-4123, Allschwil, Switzerland.
Jamie SniderThe Donnelly Centre, University of Toronto, 160 College Street, Toronto, M5S 3E1, Canada.
Igor ŠtagljarThe Donnelly Centre, University of Toronto, 160 College Street, Toronto, M5S 3E1, Canada.ORCID http://orcid.org/0000-0002-5260-3327
Jennifer KeiserSwiss Tropical and Public Health Institute, Kreuzstrasse 2, CH-4123, Allschwil, Switzerland.
Hiroyuki HiranoChemical Resource Development Research Unit, RIKEN Center for Sustainable Resource Science, 2-1 Hirosawa, Wako Saitama, 351-0198, Japan.ORCID http://orcid.org/0000-0002-0761-5548
Nobumoto WatanabeChemical Resource Development Research Unit, RIKEN Center for Sustainable Resource Science, 2-1 Hirosawa, Wako Saitama, 351-0198, Japan.ORCID http://orcid.org/0000-0002-2130-1334
Hiroyuki OsadaChemical Resource Development Research Unit, RIKEN Center for Sustainable Resource Science, 2-1 Hirosawa, Wako Saitama, 351-0198, Japan.ORCID http://orcid.org/0000-0002-3606-4925
Andrew G FraserThe Donnelly Centre, University of Toronto, 160 College Street, Toronto, M5S 3E1, Canada. andy.fraser@utoronto.ca.ORCID http://orcid.org/0000-0001-9939-6014

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Soil-transmitted helminths (STHs) are major pathogens infecting over a billion people. There are few classes of anthelmintics and there is an urgent need for new drugs. Many STHs use an unusual form of anaerobic metabolism to survive the hypoxic conditions of the host gut. This requires rhodoquinone (RQ), a quinone electron carrier. RQ is not made or used by vertebrate hosts making it an excellent therapeutic target. Here we screen 480 structural families of natural products to find compounds that kill Caenorhabditis elegans specifically when they require RQ-dependent metabolism. We identify several classes of compounds including a family of species-selective inhibitors of mitochondrial respiratory complex I. These identified complex I inhibitors have a benzimidazole core and we determine key structural requirements for activity by screening 1,280 related compounds. Finally, we show several of these compounds kill adult STHs. We suggest these species-selective complex I inhibitors are potential anthelmintics.

Indexed as

AnthelminticsCaenorhabditis elegansElectron Transport Complex IAnimalsBenzimidazolesBiological ProductsQuinonesSpecies SpecificityUbiquinoneAnthelminticsBenzimidazolesBiological ProductsElectron Transport Complex IQuinonesrhodoquinoneUbiquinone

Identifiers

PMID38719808
PMCPMC11079024

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.