Cited by 10Parasites and Host InteractionsHelminth infection and controlMollusks and Parasites Studies

Identification and characterisation of the tegument-expressed aldehyde dehydrogenase SmALDH_312 of Schistosoma mansoni, a target of disulfiram

Open access
Beutler, Mandy, Harnischfeger, Julie, Weber, Michael H.W., Hahnel, Steffen R., Quack, Thomas, Blohm, Ariane, Ueberall, Monique E., Timm, Thomas +12 more·2023·European Journal of Medicinal Chemistry

Abstract

Schistosomiasis is an infectious disease caused by blood flukes of the genus Schistosoma and affects approximately 200 million people worldwide. Since Praziquantel (PZQ) is the only drug for schistosomiasis, alternatives are needed. By a biochemical approach, we identified a tegumentally expressed aldehyde dehydrogenase (ALDH) of S. mansoni, SmALDH_312. Molecular analyses of adult parasites showed Smaldh_312 transcripts in both genders and different tissues. Physiological and cell-biological experiments exhibited detrimental effects of the drug disulfiram (DSF), a known ALDH inhibitor, on larval and adult schistosomes in vitro. DSF also reduced stem-cell proliferation and caused severe tegument damage in treated worms. In silico-modelling of SmALDH_312 and docking analyses predicted DSF binding, which we finally confirmed by enzyme assays with recombinant SmALDH_312. Furthermore, we identified compounds of the Medicine for Malaria Venture (MMV) pathogen box inhibiting SmALDH_312 activity. Our findings represent a promising starting point for further development towards new drugs for schistosomiasis.

Integrity signals

Registry

Crossref · 10.1016/j.ejmech.2023.115179

Cites

110 of 110 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

We couldn’t retrieve this paper’s full text, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Cites

Flagged first, then by citations

1 of the 111 references couldn’t be matched to a known paper.

Cited by

Sorted by citations

Authors
Beutler, M., Harnischfeger, J., Weber, M. H. W., Hahnel, S. R., Quack, T., Blohm, A., Ueberall, M. E., Timm, T., Lochnit, G., Rennar, G. A., Gallinger, T. L., Houhou, H., Rahlfs, S., Falcone, F. H., Becker, K., Schlitzer, M., Haeberlein, S., Czermak, P., Salzig, D., & Grevelding, C. G.
Affiliations
  • Justus-Liebig-Universität Gießen (DE)
  • Technische Hochschule Mittelhessen (DE)
  • Philipps University of Marburg (DE)
Corresponding author
Grevelding, Christoph G.
Venue
European Journal of Medicinal Chemistry
Publisher
Elsevier BV
Published
2023-05
Volume
251
Pages
115179
ISSN
0223-5234 (ISSN-L)
OpenAlex
W4319940593
Cited by
10
References
111
Citations by year
2026: 2 · 2025: 1 · 2024: 5 · 2023: 2
FWCI
2.34
Type
journal article
Language
en
Open access
Locations
  • European Journal of Medicinal Chemistry (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Immunology and Microbiology › Parasitology › Parasites and Host Interactions
  • Health Sciences › Veterinary › Small Animals › Helminth infection and control
  • Life Sciences › Agricultural and Biological Sciences › Insect Science › Mollusks and Parasites Studies
Keywords
Schistosoma mansoni, aldehyde dehydrogenase, disulfiram, schistosomiasis, tegument, drug target identification, enzyme inhibition, praziquantel alternatives, drug repurposing, tegument damage, stem cell proliferation
MeSH terms
Aldehyde Dehydrogenase, Animals, Disulfiram, Female, Male, Schistosoma mansoni, Schistosomiasis, Schistosomiasis mansoni

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review