Curvicollide D Isolated from the Fungus Amesia sp. Kills African Trypanosomes by Inhibiting Transcription Ortiz González, Matilde Pérez Victoria, Ignacio Ramírez Macías, Inmaculada De Pedro, Nuria Linde Rodríguez, Ángel González Menéndez, Victor M. Sánchez Martín, Victoria Martín, Jesús Soriano Lerma, Ana del Carmen Genilloud, Olga Pérez Carrasco, Virginia Vicente, Francisca Maceira, José Rodrígues Poveda, Carlos Alberto Navarro Marí, José María Reyes, Fernando Soriano, 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. 2022-06-30T10:33:23Z 2022-06-30T10:33:23Z 2022-05-29 info:eu-repo/semantics/article Ortiz-Gonzalez, M... [et al.]. Curvicollide D Isolated from the Fungus Amesia sp. Kills African Trypanosomes by Inhibiting Transcription. Int. J. Mol. Sci. 2022, 23, 6107. [https://doi.org/10.3390/ijms23116107] http://hdl.handle.net/10481/75744 10.3390/ijms23116107 eng http://creativecommons.org/licenses/by/4.0/ info:eu-repo/semantics/openAccess Atribución 4.0 Internacional MDPI