Curvicollide D Isolated from the Fungus Amesia sp. Kills African Trypanosomes by Inhibiting Transcription
Sleeping sickness or African trypanosomiasis is a serious health concern with an added socio-economic impact in sub-Saharan Africa due to direct infection in both humans and their domestic livestock. There is no vaccine available against African trypanosomes and its treatment relies only on chemothe...
| Main Authors: | , , , , , , , , , , , , , , , , , |
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| Format: | info:eu-repo/semantics/article |
| Language: | English |
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MDPI
2022
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| Online Access: | http://repositorio.ual.es/handle/10835/13713 |
| _version_ | 1789406741137457152 |
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| author | Ortiz González, Matilde Pérez-Victoria, Ignacio Ramírez Macías, María Inmaculada Pedro, Nuria de Linde Rodríguez, Ángel González-Menéndez, Víctor Sánchez Martín, Victoria Martín, Jesús Soriano-Lerma, Ana Genilloud, Olga Perez-Carrasco, Virginia Vicente, Francisca Maceira, José Rodrígues-Poveda, Carlos A. Navarro-Marí, José María Reyes, Fernando Soriano Rodríguez, Miguel García Salcedo, José Antonio |
| author_facet | Ortiz González, Matilde Pérez-Victoria, Ignacio Ramírez Macías, María Inmaculada Pedro, Nuria de Linde Rodríguez, Ángel González-Menéndez, Víctor Sánchez Martín, Victoria Martín, Jesús Soriano-Lerma, Ana Genilloud, Olga Perez-Carrasco, Virginia Vicente, Francisca Maceira, José Rodrígues-Poveda, Carlos A. Navarro-Marí, José María Reyes, Fernando Soriano Rodríguez, Miguel García Salcedo, José Antonio |
| author_sort | Ortiz González, Matilde |
| collection | DSpace |
| description | Sleeping sickness or African trypanosomiasis is a serious health concern with an added socio-economic impact in sub-Saharan Africa due to direct infection in both humans and their domestic livestock. There is no vaccine available against African trypanosomes and its treatment relies only on chemotherapy. Although the current drugs are effective, most of them are far from the modern concept of a drug in terms of toxicity, specificity and therapeutic regime. In a search for new molecules with trypanocidal activity, a high throughput screening of 2000 microbial extracts was performed. Fractionation of one of these extracts, belonging to a culture of the fungus Amesia sp., yielded a new member of the curvicollide family that has been designated as curvicollide D. The new compound showed an inhibitory concentration 50 (IC50) 16-fold lower in Trypanosoma brucei than in human cells. Moreover, it induced cell cycle arrest and disruption of the nucleolar structure. Finally, we showed that curvicollide D binds to DNA and inhibits transcription in African trypanosomes, resulting in cell death. These results constitute the first report on the activity and mode of action of a member of the curvicollide family in T. brucei. |
| format | info:eu-repo/semantics/article |
| id | oai:repositorio.ual.es:10835-13713 |
| institution | Universidad de Cuenca |
| language | English |
| publishDate | 2022 |
| publisher | MDPI |
| record_format | dspace |
| spelling | oai:repositorio.ual.es:10835-137132023-04-12T18:56:19Z Curvicollide D Isolated from the Fungus Amesia sp. Kills African Trypanosomes by Inhibiting Transcription Ortiz González, Matilde Pérez-Victoria, Ignacio Ramírez Macías, María Inmaculada Pedro, Nuria de Linde Rodríguez, Ángel González-Menéndez, Víctor Sánchez Martín, Victoria Martín, Jesús Soriano-Lerma, Ana Genilloud, Olga Perez-Carrasco, Virginia Vicente, Francisca Maceira, José Rodrígues-Poveda, Carlos A. Navarro-Marí, José María Reyes, Fernando Soriano Rodríguez, Miguel García Salcedo, José Antonio African trypanosomiasis natural products new trypanocidal molecule curvicollide D Sleeping sickness or African trypanosomiasis is a serious health concern with an added socio-economic impact in sub-Saharan Africa due to direct infection in both humans and their domestic livestock. There is no vaccine available against African trypanosomes and its treatment relies only on chemotherapy. Although the current drugs are effective, most of them are far from the modern concept of a drug in terms of toxicity, specificity and therapeutic regime. In a search for new molecules with trypanocidal activity, a high throughput screening of 2000 microbial extracts was performed. Fractionation of one of these extracts, belonging to a culture of the fungus Amesia sp., yielded a new member of the curvicollide family that has been designated as curvicollide D. The new compound showed an inhibitory concentration 50 (IC50) 16-fold lower in Trypanosoma brucei than in human cells. Moreover, it induced cell cycle arrest and disruption of the nucleolar structure. Finally, we showed that curvicollide D binds to DNA and inhibits transcription in African trypanosomes, resulting in cell death. These results constitute the first report on the activity and mode of action of a member of the curvicollide family in T. brucei. 2022-06-01T17:04:24Z 2022-06-01T17:04:24Z 2022-05-29 info:eu-repo/semantics/article 1422-0067 http://repositorio.ual.es/handle/10835/13713 10.3390/ijms23116107 en https://www.mdpi.com/1422-0067/23/11/6107 Attribution-NonCommercial-NoDerivatives 4.0 Internacional http://creativecommons.org/licenses/by-nc-nd/4.0/ info:eu-repo/semantics/openAccess MDPI |
| spellingShingle | African trypanosomiasis natural products new trypanocidal molecule curvicollide D Ortiz González, Matilde Pérez-Victoria, Ignacio Ramírez Macías, María Inmaculada Pedro, Nuria de Linde Rodríguez, Ángel González-Menéndez, Víctor Sánchez Martín, Victoria Martín, Jesús Soriano-Lerma, Ana Genilloud, Olga Perez-Carrasco, Virginia Vicente, Francisca Maceira, José Rodrígues-Poveda, Carlos A. Navarro-Marí, José María Reyes, Fernando Soriano Rodríguez, Miguel García Salcedo, José Antonio Curvicollide D Isolated from the Fungus Amesia sp. Kills African Trypanosomes by Inhibiting Transcription |
| title | Curvicollide D Isolated from the Fungus Amesia sp. Kills African Trypanosomes by Inhibiting Transcription |
| title_full | Curvicollide D Isolated from the Fungus Amesia sp. Kills African Trypanosomes by Inhibiting Transcription |
| title_fullStr | Curvicollide D Isolated from the Fungus Amesia sp. Kills African Trypanosomes by Inhibiting Transcription |
| title_full_unstemmed | Curvicollide D Isolated from the Fungus Amesia sp. Kills African Trypanosomes by Inhibiting Transcription |
| title_short | Curvicollide D Isolated from the Fungus Amesia sp. Kills African Trypanosomes by Inhibiting Transcription |
| title_sort | curvicollide d isolated from the fungus amesia sp. kills african trypanosomes by inhibiting transcription |
| topic | African trypanosomiasis natural products new trypanocidal molecule curvicollide D |
| url | http://repositorio.ual.es/handle/10835/13713 |
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