Curvicollide D Isolated from the Fungus Amesia sp. Kills African Trypanosomes by Inhibiting Transcription
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AuthorOrtiz 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 trypanosomiasisNatural productsNew trypanocidal moleculeCurvicollide D
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]
SponsorshipEuropean Union (Euronanomed programme, Reference: TARBRAINFECT); Health Carlos III as the local management institution AC18/00008; Ministry of Science, Innovation and Universities from Spain PID2020-120481RB-I00; Ministry of Education, Culture and Sport FPU 17/05413 FPU 16/05822 FPU 20/03952; University of Almeria FPI-201102 PPUENTE2021-006
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.