Idioma:

N6-methyltubercidin gives sterile cure in a cutaneous Leishmania amazonensis mouse model

Present, Cassandra ; Girão, Roberson Donola ; Lin, Cai ; Caljon, Guy ; Van Calenbergh, Serge ; Moreira, Otacilio ; Ruivo, Leonardo Alexandre de Souza ; Batista, Marcos Meuser ; Azevedo, Raquel ; Batista, Denise da Gama Jaen ; Soeiro, Maria de Nazaré Correia

Parasitology, 2024-04, Vol.151 (5), p.506-513 [Periódico revisado por pares]

Cambridge, UK: Cambridge University Press

Texto completo disponível

Citações Citado por

Enviar para

Título:
N6-methyltubercidin gives sterile cure in a cutaneous Leishmania amazonensis mouse model
Autor: Present, Cassandra ; Girão, Roberson Donola ; Lin, Cai ; Caljon, Guy ; Van Calenbergh, Serge ; Moreira, Otacilio ; Ruivo, Leonardo Alexandre de Souza ; Batista, Marcos Meuser ; Azevedo, Raquel ; Batista, Denise da Gama Jaen ; Soeiro, Maria de Nazaré Correia
Assuntos: Amines ; Animals ; Antiparasitic agents ; combination treatment ; Cytotoxicity ; Drug development ; Drug resistance ; Enzymes ; in vitro ; in vivo ; In vivo methods and tests ; Infections ; Laboratory animals ; Leishmania ; Leishmania amazonensis ; Lesions ; Macrophages ; Nucleoside analogs ; nucleoside analogues ; Nucleosides ; Parasite resistance ; Parasites ; Parasitic diseases ; Phenols ; Polymerase chain reaction ; Protozoa ; Purines ; Pyrimidines ; Regression analysis ; Skin diseases ; Skin lesions ; Toxicity ; Tropical diseases
É parte de: Parasitology, 2024-04, Vol.151 (5), p.506-513
Notas: ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
Authors contributed equally to this paper.
Descrição: Leishmania is a trypanosomatid parasite that causes skin lesions in its cutaneous form. Current therapies rely on old and expensive drugs, against which the parasites have acquired considerable resistance. Trypanosomatids are unable to synthesize purines relying on salvaging from the host, and nucleoside analogues have emerged as attractive antiparasitic drug candidates. 4-Methyl-7-β-D-ribofuranosyl-7H-pyrrolo[2,3-d]pyrimidine (CL5564), an analogue of tubercidin in which the amine has been replaced by a methyl group, demonstrates activity against Trypanosoma cruzi and Leishmania infantum. Herein, we investigated its in vitro and in vivo activity against L. amazonensis. CL5564 was 6.5-fold (P = 0.0002) more potent than milteforan™ (ML) against intracellular forms in peritoneal mouse macrophages, and highly selective, while combination with ML gave an additive effect. These results stimulated us to study the activity of CL5564 in mouse model of cutaneous Leishmania infection. BALB/c female and male mice infected by L. amazonensis treated with CL5564 (10 mg kg−1, intralesional route for five days) presented a >93% reduction of paw lesion size likely ML given orally at 40 mg kg−1, while the combination (10 + 40 mg kg−1 of CL5564 and ML, respectively) caused >96% reduction. The qPCR confirmed the suppression of parasite load, but only the combination approach reached 66% of parasitological cure. These results support additional studies with nucleoside derivatives.
Editor: Cambridge, UK: Cambridge University Press
Idioma: Inglês

Voltar para lista de resultados

Realização: Logos de Redes Sociais:

N6-methyltubercidin gives sterile cure in a cutaneous Leishmania amazonensis mouse model

Present, Cassandra ; Girão, Roberson Donola ; Lin, Cai ; Caljon, Guy ; Van Calenbergh, Serge ; Moreira, Otacilio ; Ruivo, Leonardo Alexandre de Souza ; Batista, Marcos Meuser ; Azevedo, Raquel ; Batista, Denise da Gama Jaen ; Soeiro, Maria de Nazaré Correia

Cambridge, UK: Cambridge University Press

Buscando em bases de dados remotas. Favor aguardar.