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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

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

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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]
Total Authors: 8
[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
Total Affiliations: 5
Document type: Journal article
Source: Drug Development Research; AUG 2020.
Web of Science Citations: 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)

FAPESP's process: 18/10279-6 - Selection and Optimization of New Drug Candidates for Leishmaniasis and Chagas Disease
Grantee:André Gustavo Tempone Cardoso
Support type: Regular Research Grants
FAPESP's process: 15/23403-9 - Rational Pre-Clinical Study of New Drug Candidates Against Neglected Protozoan Diseases Using Pharmacokinetic Approaches
Grantee:André Gustavo Tempone Cardoso
Support type: Regular Research Grants