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Almer\u00eda","award":["PID2020-120481RB-I00"],"award-info":[{"award-number":["PID2020-120481RB-I00"]}]},{"name":"University of Almer\u00eda","award":["FPU 17\/05413"],"award-info":[{"award-number":["FPU 17\/05413"]}]},{"name":"University of Almer\u00eda","award":["FPU 16\/05822"],"award-info":[{"award-number":["FPU 16\/05822"]}]},{"name":"University of Almer\u00eda","award":["FPU 20\/03952"],"award-info":[{"award-number":["FPU 20\/03952"]}]},{"name":"University of Almer\u00eda","award":["FPI-201102"],"award-info":[{"award-number":["FPI-201102"]}]},{"name":"University of Almer\u00eda","award":["PPUENTE2021-006"],"award-info":[{"award-number":["PPUENTE2021-006"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>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.<\/jats:p>","DOI":"10.3390\/ijms23116107","type":"journal-article","created":{"date-parts":[[2022,5,29]],"date-time":"2022-05-29T23:43:03Z","timestamp":1653867783000},"page":"6107","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Curvicollide D Isolated from the Fungus Amesia sp. Kills African Trypanosomes by Inhibiting Transcription"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9977-5735","authenticated-orcid":false,"given":"Matilde","family":"Ortiz-Gonzalez","sequence":"first","affiliation":[{"name":"Center for Intensive Mediterranean Agrosystems and Agri-Food Biotechnology (CIAIMBITAL), University of Almeria, 04001 Almer\u00eda, Spain"},{"name":"GENYO, Centre for Genomics and Oncological Research: Pfizer, University of Granada, Andalusian Regional Government, PTS Granada-Avenida de la Ilustraci\u00f3n, 18016 Granada, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4556-688X","authenticated-orcid":false,"given":"Ignacio","family":"P\u00e9rez-Victoria","sequence":"additional","affiliation":[{"name":"Fundaci\u00f3n MEDINA, Centro de Excelencia en Investigaci\u00f3n de Medicamentos Innovadores en Andaluc\u00eda, Avenida del Conocimiento 34, 18016 Granada, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9559-9180","authenticated-orcid":false,"given":"Inmaculada","family":"Ramirez-Macias","sequence":"additional","affiliation":[{"name":"GENYO, Centre for Genomics and Oncological Research: Pfizer, University of Granada, Andalusian Regional Government, PTS Granada-Avenida de la Ilustraci\u00f3n, 18016 Granada, Spain"},{"name":"Microbiology Unit, Biosanitary Research Institute IBS.Granada, University Hospital Virgen de las Nieves, 18014 Granada, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nuria","family":"de Pedro","sequence":"additional","affiliation":[{"name":"Fundaci\u00f3n MEDINA, Centro de Excelencia en Investigaci\u00f3n de Medicamentos Innovadores en Andaluc\u00eda, Avenida del Conocimiento 34, 18016 Granada, 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Oncological Research: Pfizer, University of Granada, Andalusian Regional Government, PTS Granada-Avenida de la Ilustraci\u00f3n, 18016 Granada, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3399-1835","authenticated-orcid":false,"given":"Jose A.","family":"Garcia-Salcedo","sequence":"additional","affiliation":[{"name":"GENYO, Centre for Genomics and Oncological Research: Pfizer, University of Granada, Andalusian Regional Government, PTS Granada-Avenida de la Ilustraci\u00f3n, 18016 Granada, Spain"},{"name":"Microbiology Unit, Biosanitary Research Institute IBS.Granada, University Hospital Virgen de las Nieves, 18014 Granada, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,5,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"39","DOI":"10.3389\/fimmu.2019.00039","article-title":"Clinical and Neuropathogenetic Aspects of Human African 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