In vitro and in vivo activities of DW-3-15, a commercial praziquantel derivative, against Schistosoma japonicum
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...
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| Format: | Article |
| Language: | English |
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BMC
2019-05-01
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| Series: | Parasites & Vectors |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s13071-019-3442-7 |
| _version_ | 1818159478722265088 |
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| author | Xiaoli Wang Dan Yu Chunxiang Li Tingzheng Zhan Tingting Zhang Huihui Ma Jing Xu Chaoming Xia |
| author_facet | Xiaoli Wang Dan Yu Chunxiang Li Tingzheng Zhan Tingting Zhang Huihui Ma Jing Xu Chaoming Xia |
| author_sort | Xiaoli Wang |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-11T15:46:37Z |
| format | Article |
| id | doaj.art-47a7cc73a2ce45969895e80a5f903a28 |
| institution | Directory Open Access Journal |
| issn | 1756-3305 |
| language | English |
| last_indexed | 2024-12-11T15:46:37Z |
| publishDate | 2019-05-01 |
| publisher | BMC |
| record_format | Article |
| series | Parasites & Vectors |
| spelling | doaj.art-47a7cc73a2ce45969895e80a5f903a282022-12-22T00:59:41ZengBMCParasites & Vectors1756-33052019-05-0112111310.1186/s13071-019-3442-7In vitro and in vivo activities of DW-3-15, a commercial praziquantel derivative, against Schistosoma japonicumXiaoli Wang0Dan Yu1Chunxiang Li2Tingzheng Zhan3Tingting Zhang4Huihui Ma5Jing Xu6Chaoming Xia7Department of Parasitology, Medical College of Soochow UniversityDepartment of Parasitology, Medical College of Soochow UniversityDepartment of Parasitology, Medical College of Soochow UniversityDepartment of Parasitology, Medical College of Soochow UniversityDepartment of Parasitology, Medical College of Soochow UniversityDepartment of Parasitology, Medical College of Soochow UniversityDepartment of Parasitology, Medical College of Soochow UniversityDepartment of Parasitology, Medical College of Soochow UniversityAbstract 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.http://link.springer.com/article/10.1186/s13071-019-3442-7PraziquantelSchistosoma japonicumSchistosomicide |
| spellingShingle | Xiaoli Wang Dan Yu Chunxiang Li Tingzheng Zhan Tingting Zhang Huihui Ma Jing Xu Chaoming Xia In vitro and in vivo activities of DW-3-15, a commercial praziquantel derivative, against Schistosoma japonicum Parasites & Vectors Praziquantel Schistosoma japonicum Schistosomicide |
| title | In vitro and in vivo activities of DW-3-15, a commercial praziquantel derivative, against Schistosoma japonicum |
| title_full | In vitro and in vivo activities of DW-3-15, a commercial praziquantel derivative, against Schistosoma japonicum |
| title_fullStr | In vitro and in vivo activities of DW-3-15, a commercial praziquantel derivative, against Schistosoma japonicum |
| title_full_unstemmed | In vitro and in vivo activities of DW-3-15, a commercial praziquantel derivative, against Schistosoma japonicum |
| title_short | In vitro and in vivo activities of DW-3-15, a commercial praziquantel derivative, against Schistosoma japonicum |
| title_sort | in vitro and in vivo activities of dw 3 15 a commercial praziquantel derivative against schistosoma japonicum |
| topic | Praziquantel Schistosoma japonicum Schistosomicide |
| url | http://link.springer.com/article/10.1186/s13071-019-3442-7 |
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