Pyrvinium Pamoate and Structural Analogs Are Early Macrofilaricide Leads
Onchocerciasis and lymphatic filariasis are neglected tropical diseases caused by infection with filarial worms. Annual or biannual mass drug administration with microfilaricidal drugs that kill the microfilarial stages of the parasites has helped reduce infection rates and thus prevent transmission...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-02-01
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| Series: | Pharmaceuticals |
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| Online Access: | https://www.mdpi.com/1424-8247/15/2/189 |
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| author | Emma L. Gunderson Clifford Bryant Christina A. Bulman Chelsea Fischer Mona Luo Ian Vogel Kee-Chong Lim Shabnam Jawahar Nancy Tricoche Denis Voronin Christopher Corbo Rene B. Ayiseh Faustin P. T. Manfo Glory E. Mbah Fidelis Cho-Ngwa Brenda Beerntsen Adam R. Renslo Sara Lustigman Judy A. Sakanari |
| author_facet | Emma L. Gunderson Clifford Bryant Christina A. Bulman Chelsea Fischer Mona Luo Ian Vogel Kee-Chong Lim Shabnam Jawahar Nancy Tricoche Denis Voronin Christopher Corbo Rene B. Ayiseh Faustin P. T. Manfo Glory E. Mbah Fidelis Cho-Ngwa Brenda Beerntsen Adam R. Renslo Sara Lustigman Judy A. Sakanari |
| author_sort | Emma L. Gunderson |
| collection | DOAJ |
| description | Onchocerciasis and lymphatic filariasis are neglected tropical diseases caused by infection with filarial worms. Annual or biannual mass drug administration with microfilaricidal drugs that kill the microfilarial stages of the parasites has helped reduce infection rates and thus prevent transmission of both infections. However, success depends on high population coverage that is maintained for the duration of the adult worm’s lifespan. Given that these filarial worms can live up to 14 years in their human hosts, a macrofilaricidal drug would vastly accelerate elimination efforts. Here, we have evaluated the repurposed drug pyrvinium pamoate as well as newly synthesized analogs of pyrvinium for their efficacy against filarial worms in vitro and in vivo. We found that pyrvinium pamoate, tetrahydropyrvinium and one of the analogs were highly potent in inhibiting worms in in vitro whole-worm screening assays, and that all three compounds reduced female worm fecundity and inhibited embryogenesis in the <i>Brugia pahangi</i>-gerbil in vivo model of infection. |
| first_indexed | 2024-03-09T21:15:49Z |
| format | Article |
| id | doaj.art-47f08033f00a440f8fc6a2eb661e1414 |
| institution | Directory Open Access Journal |
| issn | 1424-8247 |
| language | English |
| last_indexed | 2024-03-09T21:15:49Z |
| publishDate | 2022-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceuticals |
| spelling | doaj.art-47f08033f00a440f8fc6a2eb661e14142023-11-23T21:34:25ZengMDPI AGPharmaceuticals1424-82472022-02-0115218910.3390/ph15020189Pyrvinium Pamoate and Structural Analogs Are Early Macrofilaricide LeadsEmma L. Gunderson0Clifford Bryant1Christina A. Bulman2Chelsea Fischer3Mona Luo4Ian Vogel5Kee-Chong Lim6Shabnam Jawahar7Nancy Tricoche8Denis Voronin9Christopher Corbo10Rene B. Ayiseh11Faustin P. T. Manfo12Glory E. Mbah13Fidelis Cho-Ngwa14Brenda Beerntsen15Adam R. Renslo16Sara Lustigman17Judy A. Sakanari18Department of Pharmaceutical Chemistry, University of California San Francisco, San Francisco, CA 94158, USADepartment of Pharmaceutical Chemistry, University of California San Francisco, San Francisco, CA 94158, USADepartment of Pharmaceutical Chemistry, University of California San Francisco, San Francisco, CA 94158, USADepartment of Pharmaceutical Chemistry, University of California San Francisco, San Francisco, CA 94158, USADepartment of Pharmaceutical Chemistry, University of California San Francisco, San Francisco, CA 94158, USADepartment of Pharmaceutical Chemistry, University of California San Francisco, San Francisco, CA 94158, USADepartment of Pharmaceutical Chemistry, University of California San Francisco, San Francisco, CA 94158, USAMolecular Parasitology, New York Blood Center, Lindsley F. Kimball Research Institute, New York, NY 10065, USAMolecular Parasitology, New York Blood Center, Lindsley F. Kimball Research Institute, New York, NY 10065, USAMolecular Parasitology, New York Blood Center, Lindsley F. Kimball Research Institute, New York, NY 10065, USADepartment of Biological Sciences, Wagner College, Staten Island, NY 10301, USAANDI Centre of Excellence for Onchocerciasis Drug Research, Biotechnology Unit, Faculty of Science, University of Buea, Buea P.O. Box 63, CameroonANDI Centre of Excellence for Onchocerciasis Drug Research, Biotechnology Unit, Faculty of Science, University of Buea, Buea P.O. Box 63, CameroonANDI Centre of Excellence for Onchocerciasis Drug Research, Biotechnology Unit, Faculty of Science, University of Buea, Buea P.O. Box 63, CameroonANDI Centre of Excellence for Onchocerciasis Drug Research, Biotechnology Unit, Faculty of Science, University of Buea, Buea P.O. Box 63, CameroonDepartment of Veterinary Pathobiology, University of Missouri-Columbia, Columbia, MO 65211, USADepartment of Pharmaceutical Chemistry, University of California San Francisco, San Francisco, CA 94158, USAMolecular Parasitology, New York Blood Center, Lindsley F. Kimball Research Institute, New York, NY 10065, USADepartment of Pharmaceutical Chemistry, University of California San Francisco, San Francisco, CA 94158, USAOnchocerciasis and lymphatic filariasis are neglected tropical diseases caused by infection with filarial worms. Annual or biannual mass drug administration with microfilaricidal drugs that kill the microfilarial stages of the parasites has helped reduce infection rates and thus prevent transmission of both infections. However, success depends on high population coverage that is maintained for the duration of the adult worm’s lifespan. Given that these filarial worms can live up to 14 years in their human hosts, a macrofilaricidal drug would vastly accelerate elimination efforts. Here, we have evaluated the repurposed drug pyrvinium pamoate as well as newly synthesized analogs of pyrvinium for their efficacy against filarial worms in vitro and in vivo. We found that pyrvinium pamoate, tetrahydropyrvinium and one of the analogs were highly potent in inhibiting worms in in vitro whole-worm screening assays, and that all three compounds reduced female worm fecundity and inhibited embryogenesis in the <i>Brugia pahangi</i>-gerbil in vivo model of infection.https://www.mdpi.com/1424-8247/15/2/189repurposed drugspyrvinium pamoatefilarial diseasesmacrofilaricides |
| spellingShingle | Emma L. Gunderson Clifford Bryant Christina A. Bulman Chelsea Fischer Mona Luo Ian Vogel Kee-Chong Lim Shabnam Jawahar Nancy Tricoche Denis Voronin Christopher Corbo Rene B. Ayiseh Faustin P. T. Manfo Glory E. Mbah Fidelis Cho-Ngwa Brenda Beerntsen Adam R. Renslo Sara Lustigman Judy A. Sakanari Pyrvinium Pamoate and Structural Analogs Are Early Macrofilaricide Leads Pharmaceuticals repurposed drugs pyrvinium pamoate filarial diseases macrofilaricides |
| title | Pyrvinium Pamoate and Structural Analogs Are Early Macrofilaricide Leads |
| title_full | Pyrvinium Pamoate and Structural Analogs Are Early Macrofilaricide Leads |
| title_fullStr | Pyrvinium Pamoate and Structural Analogs Are Early Macrofilaricide Leads |
| title_full_unstemmed | Pyrvinium Pamoate and Structural Analogs Are Early Macrofilaricide Leads |
| title_short | Pyrvinium Pamoate and Structural Analogs Are Early Macrofilaricide Leads |
| title_sort | pyrvinium pamoate and structural analogs are early macrofilaricide leads |
| topic | repurposed drugs pyrvinium pamoate filarial diseases macrofilaricides |
| url | https://www.mdpi.com/1424-8247/15/2/189 |
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