RT Journal Article
T1 Curvicollide D Isolated from the Fungus Amesia sp. Kills African Trypanosomes by Inhibiting Transcription.
A1 Ortiz-Gonzalez, Matilde
A1 Perez-Victoria, Ignacio
A1 Ramirez-Macias, Inmaculada
A1 de Pedro, Nuria
A1 Linde-Rodriguez, Angel
A1 Gonzalez-Menendez, Victor
A1 Sanchez-Martin, Victoria
A1 Martin, Jesus
A1 Soriano-Lerma, Ana
A1 Genilloud, Olga
A1 Perez-Carrasco, Virginia
A1 Vicente, Francisca
A1 Maceira, Jose
A1 Rodrigues-Poveda, Carlos A
A1 Navarro-Mari, Jose Maria
A1 Reyes, Fernando
A1 Soriano, Miguel
A1 Garcia-Salcedo, Jose A
K1 African trypanosomiasis
K1 curvicollide D
K1 natural products
K1 new trypanocidal molecule
AB 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.
PB MDPI AG
YR 2022
FD 2022-05-27
LK http://hdl.handle.net/10668/21161
UL http://hdl.handle.net/10668/21161
LA en
NO Ortiz-Gonzalez M, Pérez-Victoria I, Ramirez-Macias I, de Pedro N, Linde-Rodriguez A, González-Menéndez V, el al.  Curvicollide D Isolated from the Fungus Amesia sp. Kills African Trypanosomes by Inhibiting Transcription. Int J Mol Sci. 2022 May 29;23(11):6107.
NO This study was funded by the European Union (Euronanomed programme, Reference:TARBRAINFECT), the Health Carlos III as the local management institution (Reference: AC18/00008)and by Ministry of Science, Innovation and Universities from Spain (PID2020-120481RB-I00 to M.S.).A.S.-L., V.S.-M. and V.P.-C. were supported by fellowships from the Ministry of Education, Cultureand Sport (FPU 17/05413, FPU 16/05822 and FPU 20/03952, respectively). M.O.-G. was supportedby a fellowship from the University of Almería (FPI-201102 and PPUENTE2021-006). The resultspresented in this article are part of M.O.-G.’s doctoral thesis
DS RISalud
RD Jul 1, 2025