Please use this identifier to cite or link to this item: https://www.arca.fiocruz.br/handle/icict/30120
Title: Triphenylmethane Derivatives Have High In Vitro and In Vivo Activity against the Main Causative Agents of Cutaneous Leishmaniasis
Authors: Pietra, Renata Celi Carvalho de Souza
Rodrigues, Lucas Fonseca
Teixeira, Eliane de Moraes
Fried, Levi
Lefkove, Benjamin
Rabello, Ana Lucia Teles
Arbiser, Jack
Ferreira, Lucas Antônio Miranda
Fernandes, Ana Paula
Affilliation: Universidade Federal de Minas Gerais. Departamento de Análises Clínicas e Toxicológicas.Belo Horizonte, MG, Brazil
Universidade Federal de Minas Gerais. Departamento de Análises Clínicas e Toxicológicas.Belo Horizonte, MG, Brazil
Fundação Oswaldo Cruz. Instituto René Rachou. Laboratório de Pesquisa Clínica. Belo Horizonte, MG, Brasil.
Department of Dermatology. Emory University School of Medicine. Atlanta, Georgia, United States of America.
Department of Dermatology. Emory University School of Medicine. Atlanta, Georgia, United States of America.
Fundação Oswaldo Cruz. Instituto René Rachou. Laboratório de Pesquisa Clínica. Belo Horizonte, MG, Brasil.
Department of Dermatology. Emory University School of Medicine. Atlanta, Georgia, United States of America.
Universidade Federal de Minas Gerais. Departamento de Análises Clínicas e Toxicológicas.Belo Horizonte, MG, Brazil
Universidade Federal de Minas Gerais. Departamento de Análises Clínicas e Toxicológicas.Belo Horizonte, MG, Brazil
Abstract: The current standard of care for cutaneous leishmaniasis (CL) is organic antimonial compounds, but the administration of these compounds is complicated by a low therapeutic - toxic index, as well as parenteral administration. Thus, there is an urgent need for the development of new and inexpensive therapies for the treatment of CL. In this study, we evaluate the activity of the triphenylmethane (TPM) class of compounds against three species of Leishmania which are pathogenic in humans. The TPM have a history of safe use in humans, dating back to the use of the original member of this class, gentian violet (GV), from the early 20th century. Initially, the in vitro efficacy against Leishmania (Viannia) braziliensis, L. (Leishmania) amazonensis and L. (L.) major of 9 newly synthesized TPM, in addition to GV, was tested. Inhibitory concentrations (IC) IC50 of 0.025 to 0.84 µM had been found in promastigotes in vitro assays. The four most effective compounds were then tested in amastigote intracellular assays, resulting in IC50 of 0.10 to 1.59 µM. A high degree of selectivity of antiparasitic activity over toxicity to mammalian cells was observed. Afterwards, GV and TPM 6 were tested in a topical formulation in mice infected with L. (L.) amazonensis leading to elimination of parasite burdens at the site of lesion/infection. These results demonstrated that TPM present significant anti-leishmanial activities and provide a rationale for human clinical trials of GV and other TPM. TPM are inexpensive and safe, thus using them for treatment of CL may have a major impact on public health.
Keywords: Parasitic diseases
Leishmania
Promastigotes
Macrophages
Amastigotes
Cytotoxicity
Leishmaniasis
MTT assay
keywords: doenças parasitarias
leishmaniose
Promastigotas
Macrofagos
Amastigotas
Issue Date: 2013
Publisher: Public Library of Science
Citation: PIETRA, Renata Celi Carvalho de Souza et al. Triphenylmethane Derivatives Have High In Vitro and In Vivo Activity against the Main Causative Agents of Cutaneous Leishmaniasis. PLoS One, v. 8, n. 1, e51864, 2013
DOI: 10.1371/journal.pone.0051864
ISSN: 1932-6203
Copyright: open access
Appears in Collections:MG - IRR - Artigos de Periódicos

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