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In vitro and in vivo activities of DW-3-15, a commercial praziquantel derivative, against Schistosoma japonicum
- Source :
- Parasites & Vectors, Parasites & Vectors, Vol 12, Iss 1, Pp 1-13 (2019)
- Publication Year :
- 2018
-
Abstract
- Background Schistosomiasis is a debilitating neglected tropical disease that affects approximately 190 million people around the world. Praziquantel (PZQ) is the only drug available for use against all Schistosoma species. Although PZQ has a high efficacy, recognized concerns have prompted the development of new, alternative drugs for repeated use in endemic areas where PZQ efficacy against strains of Schistosoma is reduced. A hybrid drug containing different pharmacophores within a single molecule is a promising strategy. Our earlier in vivo studies showed the significant antiparasitic activity of a praziquantel derivative, DW-3-15, against Schistosoma japonicum. In the present study, DW-3-15 was synthesized in large amounts by a pharmaceutical company and its schistosomicidal efficacy and stability were further confirmed. Parameters such as parasite viability, pairing and oviposition were evaluated in vitro. An in vivo study was conducted to assess the effect of commercial DW-3-15 on worm burden, egg production and diameter of granulomas. Additionally, to gain insight into the mechanism of action for DW-3-15, morphological changes in the tegument of S. japonicum were also examined. Results The in vitro study showed the antiparasitic activity of DW-3-15 against S. japonicum, with significant reductions in viability of adult and juvenile worms, worm pairings and egg output. Compared to PZQ, DW-3-15 induced similar ultrastructural changes and evident destruction of the tegument surface in male worms. In vivo, the oral administration of DW-3-15 at a dose of 400 mg/kg per day for five consecutive days in mice significantly reduced the total worm burden and number of eggs in the liver. Histological analysis of the livers showed a marked reduction in the average diameter of the egg granuloma. Conclusions Our findings suggest that DW-3-15, a PZQ derivative with the prospect of commercial production, can be developed as a potential promising schistosomicide. Electronic supplementary material The online version of this article (10.1186/s13071-019-3442-7) contains supplementary material, which is available to authorized users.
- Subjects :
- 0301 basic medicine
Male
Schistosomicide
030231 tropical medicine
Administration, Oral
Schistosomiasis
Pharmacology
Praziquantel
Schistosoma japonicum
lcsh:Infectious and parasitic diseases
03 medical and health sciences
Schistosomicides
0302 clinical medicine
In vivo
parasitic diseases
medicine
Helminths
Animals
Humans
lcsh:RC109-216
Parasite Egg Count
Schistosoma
Mice, Inbred ICR
biology
Research
Viral tegument
biology.organism_classification
medicine.disease
030104 developmental biology
Infectious Diseases
Parasitology
Liver
Schistosomiasis japonica
Female
medicine.drug
Subjects
Details
- ISSN :
- 17563305
- Volume :
- 12
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Parasitesvectors
- Accession number :
- edsair.doi.dedup.....762a86968d41be4ee2f1df456da55a28