Identification and characterisation of the tegument-expressed aldehyde dehydrogenase SmALDH_312 of Schistosoma mansoni, a target of disulfiram
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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.
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DIS effectively targets the tegument-expressed ALDH SmALDH_312, demonstrating potent activity against Schistosoma mansoni.
“In addition, the drug effectively targets the tegument-expressed ALDH SmALDH_312, demonstrating potent activity against Schistosoma mansoni.116”
From Off-label and repurposed use of disulfiram beyond alcohol dependence: A systematic review of clinical and preclinical evidence (2026) · cites this paper as [116]
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1 of the 111 references couldn’t be matched to a known paper.
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Self-citationRecent advances in medicinal chemistry of Neglected Tropical Diseases (NTDs)
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Self-citationMechanisms of Arachidonic Acid In Vitro Schistosomicidal Potential
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Self-citation
- 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.
- ORCID
- 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
- hybrid
- doi.org
- Licence
- 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
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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.
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