Por favor, use este identificador para citar o enlazar este ítem:
https://www.arca.fiocruz.br/handle/icict/63192
Tipo
ArtículoDerechos de autor
Acceso abierto
Colecciones
Metadatos
Mostrar el registro completo del ítem
NOVEL 2,5-DIKETOPIPERAZINES WITH IN VITRO ACTIVITIES AGAINST PROTOZOAN PARASITES OF TROPICAL DISEASES
Cyclic dipeptides
Malaria
Chagas disease
Leishmaniasis
Plasmodium falciparum
Trypanosoma cruzi
Leishmania infantum
Autor
Afiliación
Oswaldo Cruz Foundation. René Rachou Institute. Laboratory of Immunopathology. Belo Horizonte, MG, Brazil.
Oswaldo Cruz Foundation. René Rachou Institute. Laboratory of Immunopathology. Belo Horizonte, MG, Brazil.
Oswaldo Cruz Foundation. René Rachou Institute. Laboratory of Immunopathology. Belo Horizonte, MG, Brazil.
Oswaldo Cruz Foundation. René Rachou Institute. Laboratory of Functional Genomics of Parasites. Belo Horizonte, MG, Brazil.
Oswaldo Cruz Foundation. René Rachou Institute. Laboratory of Functional Genomics of Parasites. Belo Horizonte, MG, Brazil.
Oswaldo Cruz Foundation. René Rachou Institute. Laboratory of Functional Genomics of Parasites. Belo Horizonte, MG, Brazil.
Laboratory of Natural Product Chemistry Studies and Organic Synthesis. Federal University of Viçosa. Viçosa, MG, Brazil
Laboratory of Natural Product Chemistry Studies and Organic Synthesis. Federal University of Viçosa. Viçosa, MG, Brazil
Laboratory of Natural Product Chemistry Studies and Organic Synthesis. Federal University of Viçosa. Viçosa, MG, Brazil
Oswaldo Cruz Foundation. René Rachou Institute. LLaboratory of Bioactive Natural Product Chemistry. Belo Horizonte, MG, Brazil.
Oswaldo Cruz Foundation. René Rachou Institute. Laboratory of Immunopathology. Belo Horizonte, MG, Brazil.
Oswaldo Cruz Foundation. René Rachou Institute. Laboratory of Immunopathology. Belo Horizonte, MG, Brazil.
Oswaldo Cruz Foundation. René Rachou Institute. Laboratory of Functional Genomics of Parasites. Belo Horizonte, MG, Brazil.
Oswaldo Cruz Foundation. René Rachou Institute. Laboratory of Functional Genomics of Parasites. Belo Horizonte, MG, Brazil.
Oswaldo Cruz Foundation. René Rachou Institute. Laboratory of Functional Genomics of Parasites. Belo Horizonte, MG, Brazil.
Laboratory of Natural Product Chemistry Studies and Organic Synthesis. Federal University of Viçosa. Viçosa, MG, Brazil
Laboratory of Natural Product Chemistry Studies and Organic Synthesis. Federal University of Viçosa. Viçosa, MG, Brazil
Laboratory of Natural Product Chemistry Studies and Organic Synthesis. Federal University of Viçosa. Viçosa, MG, Brazil
Oswaldo Cruz Foundation. René Rachou Institute. LLaboratory of Bioactive Natural Product Chemistry. Belo Horizonte, MG, Brazil.
Resumen en ingles
Malaria, Chagas disease, and leishmaniasis are tropical diseases caused by protozoan parasites of the genera Plasmodium, Trypanosoma and Leishmania, respectively. These diseases constitute a major burden on public health in several regions worldwide, mainly affecting low-income populations in economically poor countries. Severe side effects of currently available drug treatments and the emergence of resistant parasites need to be addressed by the development of novel drug candidates. Natural 2,5-Diketopiperazines (2,5-DKPs) constitute N-heterocyclic secondary metabolites with a wide range of biological activities of medicinal interest. Its structural and physicochemical properties make the 2,5-DKP ring a versatile, peptide-like, and stable pharmacophore attractive for synthetic drug design. In the present work, twenty-three novel synthetic 2,5-DKPs, previously synthesized through the versatile Ugi multicomponent reaction, were assayed for their anti-protozoal activities against P. falciparum, T. cruzi, and L. infantum. Some of the 2,5-DKPs have shown promising activities against the target protozoans, with inhibitory concentrations (IC50) ranging from 5.4 to 9.5 µg/mL. The most active compounds also show low cytotoxicity (CC50), affording selectivity indices ≥ 15. Results allowed for observing a clear relationship between the substitution pattern at the aromatic rings of the 2,5-DKPs and their corresponding anti-Plasmodium activity. Finally, calculated drug-like properties of the compounds revealed points for further structure optimization of promising drug candidates.
Palabras clave en ingles
DiketopiperazinesCyclic dipeptides
Malaria
Chagas disease
Leishmaniasis
Plasmodium falciparum
Trypanosoma cruzi
Leishmania infantum
Compartir