| Texto completo | |
| Autor(es): |
Mesquita, Juliana Tonini
;
Moura, Gabriel Candido
;
Cavalcante, Taina
;
Yokoyama Yasunaka, Jenicer Kazumi Umada
;
Peres, Manoel Aparecido
;
Blanes Angeli, Claudia
;
Taniwaki, Noemi Nosomi
;
Simonsen Stolf, Beatriz
;
Palmisano, Giuseppe
;
Katzin, Alejandro Miguel
Número total de Autores: 10
|
| Tipo de documento: | Artigo Científico |
| Fonte: | Antimicrobial Agents and Chemotherapy; v. N/A, p. 17-pg., 2025-10-07. |
| Resumo | |
Leishmaniasis is a parasitic disease caused by several species of the genus Leishmania, considered one of the most dangerous neglected tropical diseases in the world. Treatment options are limited and toxicity exists, requiring an urgent search for new therapies. Leishmania differs from mammalian cells by having unique mitochondria, which have been considered an important therapeutic target. Ubiquinone is found in the inner membrane of mitochondria and plays a critical role in the electron transport chain, which is essential for cell viability. The combination of buparvaquone and 4-nitrobenzoate seems an interesting option due to their action on these targets. The aim of the present work was to investigate the effects of this combination against Leishmania (Leishmania) amazonensis infections in vitro and in vivo and to elucidate the possible mechanism of action of 4-nitrobenzoate. The results showed that the drug combination tested in promastigotes has an additive or indifferent effect. In the intracellular amastigotes, when buparvaquone was tested with fixed concentrations of 4-nitrobenzoate, concentrations that had no effect alone potentiated the effect of buparvaquone by two to four times. The mechanism of action of 4-nitrobenzoate in promastigote forms suggests a reduction in ubiquinone 6 levels, an alteration in mitochondrial membrane potential, and an increase in reactive oxygen species. In vivo treatment with a topical formulation (buparvaquone 0.1% and 4-nitrobenzoate 0.1%) in infected mice showed a reduction in parasite burden of 57% compared to the control group, suggesting that this combination may represent a promising therapeutic strategy for future treatment of this disease. (AU) | |
| Processo FAPESP: | 24/09997-2 - Biossíntese de isoprenóides em Plasmodium falciparum. Avaliação de possíveis alvos para a obtenção de novas drogas antimaláricas. |
| Beneficiário: | Alejandro Miguel Katzin |
| Modalidade de apoio: | Auxílio à Pesquisa - Regular |
| Processo FAPESP: | 17/22452-1 - Biossíntese de isoprenóides em Plasmodium falciparum: avaliação de possíveis alvos para a obtenção de novas drogas antimaláricas |
| Beneficiário: | Alejandro Miguel Katzin |
| Modalidade de apoio: | Auxílio à Pesquisa - Temático |
| Processo FAPESP: | 20/04923-0 - Glicosilação do SARS-CoV-2 para identificação das características estruturais da COVID-19 |
| Beneficiário: | Giuseppe Palmisano |
| Modalidade de apoio: | Auxílio à Pesquisa - Regular |
| Processo FAPESP: | 21/01877-0 - Estudo da inibição da biossíntese de ubiquinona em Leishmania (L.) amazonensis como estratégia na descoberta de novos alvos terapêuticos |
| Beneficiário: | Juliana Tonini Mesquita |
| Modalidade de apoio: | Bolsas no Brasil - Pós-Doutorado |
| Processo FAPESP: | 18/15549-1 - Modificações pós-traducionais nos processos biológicos e no diagnóstico da Doença de Chagas: novas abordagens metodológicas e implicações biológicas |
| Beneficiário: | Giuseppe Palmisano |
| Modalidade de apoio: | Auxílio à Pesquisa - Jovens Pesquisadores - Fase 2 |