Busca avançada
Ano de início
(Referência obtida automaticamente do Web of Science, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores.)

Repurposing topical triclosan for cutaneous leishmaniasis: Preclinical efficacy in a murineLeishmania (L.) amazonensismodel

Texto completo
Mesquita, Juliana Tonini [1] ; Romanelli, Maiara Maria [1] ; Trinconi Trinconi, Cristiana de Melo C. M. [2] ; Guerra, Juliana Mariotti [3] ; Taniwaki, Noemi Nosomi [4] ; Bortolin Uliana, Silvia Reni [2] ; Reimao, Juliana Quero [5] ; Tempone, Andre Gustavo [1]
Número total de Autores: 8
Afiliação do(s) autor(es):
[1] Adolfo Lutz Inst, Ctr Parasitol & Mycol, Sao Paulo - Brazil
[2] Univ Sao Paulo, Inst Ciencias Biomed, Dept Parasitol, Sao Paulo - Brazil
[3] Adolfo Lutz Inst, Ctr Patol, Sao Paulo - Brazil
[4] Adolfo Lutz Inst, Ctr Interdisciplinary Proceedings, Sao Paulo - Brazil
[5] Fac Med Jundiai, Dept Morfol & Patol Bas, Jundiai - Brazil
Número total de Afiliações: 5
Tipo de documento: Artigo Científico
Fonte: Drug Development Research; AUG 2020.
Citações Web of Science: 0

Leishmaniasisremains an important neglected tropical infection caused by the protozoanLeishmaniaand affects 12 million people in 98 countries. The treatment is limited with severe adverse effects. In the search for new therapies, the drug repositioning and combination therapy have been successfully applied to neglected diseases. The aim of the present study was to evaluate the in vitro and in vivo anti-Leishmania(Leishmania)amazonensispotential of triclosan, an approved topical antimicrobial agent used for surgical procedures. in vitro phenotypic studies of drug-treated parasites were performed to evaluate the lethal action of triclosan, accompanied by an isobolographic ex-vivo analysis with the association of triclosan and miltefosine. The results showed that triclosan has activity againstL.(L.)amazonensisintracellular amastigotes, with a 50% inhibitory concentration of 16 mu M. By using fluorescent probes and transmission electron microscopy, a pore-forming activity of triclosan toward the parasite plasma membrane was demonstrated, leading to depolarization of the mitochondrial membrane potential and reduction of the reactive oxygen species levels in the extracellular promastigotes. The in vitro interaction between triclosan and miltefosine in the combination therapy assay was classified as additive against intracellular amastigotes.Leishmania-infected mice were treated with topical triclosan (1% base cream for 14 consecutive days), and showed 89% reduction in the parasite burden. The obtained results contribute to the investigation of new alternatives for the treatment of cutaneous leishmaniasis and suggest that the coadministration of triclosan and miltefosine should be investigated in animal models. (AU)

Processo FAPESP: 18/10279-6 - Seleção e Otimização de Novos Candidatos a Fármacos para Leishmaniose e Doença de Chagas
Beneficiário:André Gustavo Tempone Cardoso
Modalidade de apoio: Auxílio à Pesquisa - Regular
Processo FAPESP: 15/23403-9 - Estudo Pré-Clínico Racional de Novos Candidatos a Fármacos em Protozooses Negligenciadas Utilizando Abordagens Farmacocinéticas
Beneficiário:André Gustavo Tempone Cardoso
Modalidade de apoio: Auxílio à Pesquisa - Regular