ArticlePLoS pathogens2023
Oxamniquine derivatives overcome Praziquantel treatment limitations for Schistosomiasis.
Article in PLoS pathogens, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 19 citations in OpenAlex.
- Toward transgenic multicellular parasites: CRISPR-Cas12a germline editing ofScience advances · 2026Article
- Pharmacological assessment of drugs retained in the 1Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- IL-22 modulates STAT3/β-catenin/let-7a signaling and hepatic granulomas in Schistosoma mansoni infection: versus praziquantel and combination treatment.Molecular biology reports · 2026Article
- Article
- mRNA vaccines encoding variant forms of Sm-TSP-2 confer protective immunity against Schistosoma mansoni.NPJ vaccines · 2025Article
- Highly accurate protein structure prediction-based virtual docking pipeline accelerating the identification of anti-schistosomal compounds.PLoS pathogens · 2025Article
- Development of a Novel Compound Effective Against Juvenile, Adult, and Drug-ResistantPharmaceutics · 2025Review
- Therapeutic challenges of schistosomiasis: mechanisms of action and current limitations.Journal of parasitic diseases : official organ of the Indian Society for Parasitology · 2025Review
- Yinchenhao Decoction Combined with Praziquantel Ameliorates Inflammation and Hepatic Fibrosis in Schistosoma japonicum-Infected Mice.Current medical science · 2025Article
- Considering ivermectin for treatment of schistosomiasis.Parasitology research · 2024Article
- Progress interrogating TRPMPZQ as the target of praziquantel.PLoS neglected tropical diseases · 2024Review
- Schistosomiasis.Advances in experimental medicine and biology · 2024Review
- Oxamniquine derivatives overcome Praziquantel treatment limitations for Schistosomiasis.PLoS pathogens · 2023Article
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Human schistosomiasis is a neglected tropical disease caused by Schistosoma mansoni, S. haematobium, and S. japonicum. Praziquantel (PZQ) is the method of choice for treatment. Due to constant selection pressure, there is an urgent need for new therapies for schistosomiasis. Previous treatment of S. mansoni included the use of oxamniquine (OXA), a drug that is activated by a schistosome sulfotransferase (SULT). Guided by data from X-ray crystallography and Schistosoma killing assays more than 350 OXA derivatives were designed, synthesized, and tested. We were able to identify CIDD-0150610 and CIDD-0150303 as potent derivatives in vitro that kill (100%) of all three Schistosoma species at a final concentration of 71.5 μM. We evaluated the efficacy of the best OXA derivates in an in vivo model after treatment with a single dose of 100 mg/kg by oral gavage. The highest rate of worm burden reduction was achieved by CIDD -150303 (81.8%) against S. mansoni, CIDD-0149830 (80.2%) against S. haematobium and CIDD-066790 (86.7%) against S. japonicum. We have also evaluated the ability of the derivatives to kill immature stages since PZQ does not kill immature schistosomes. CIDD-0150303 demonstrated (100%) killing for all life stages at a final concentration of 143 μM in vitro and effective reduction in worm burden in vivo against S. mansoni. To understand how OXA derivatives fit in the SULT binding pocket, X-ray crystal structures of CIDD-0150303 and CIDD-0150610 demonstrate that the SULT active site will accommodate further modifications to our most active compounds as we fine tune them to increase favorable pharmacokinetic properties. Treatment with a single dose of 100 mg/kg by oral gavage with co-dose of PZQ + CIDD-0150303 reduced the worm burden of PZQ resistant parasites in an animal model by 90.8%. Therefore, we conclude that CIDD-0150303, CIDD-0149830 and CIDD-066790 are novel drugs that overcome some of PZQ limitations, and CIDD-0150303 can be used with PZQ in combination therapy.
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