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Triphenylmethane Derivatives Have High In Vitro and In Vivo Activity against the Main Causative Agents of Cutaneous Leishmaniasis
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 t...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3544846/ https://www.ncbi.nlm.nih.gov/pubmed/23341885 http://dx.doi.org/10.1371/journal.pone.0051864 |
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author | de Souza Pietra, Renata Celi Carvalho Rodrigues, Lucas Fonseca Teixeira, Eliane Fried, Levi Lefkove, Benjamin Rabello, Ana Arbiser, Jack Ferreira, Lucas Antônio Miranda Fernandes, Ana Paula |
author_facet | de Souza Pietra, Renata Celi Carvalho Rodrigues, Lucas Fonseca Teixeira, Eliane Fried, Levi Lefkove, Benjamin Rabello, Ana Arbiser, Jack Ferreira, Lucas Antônio Miranda Fernandes, Ana Paula |
author_sort | de Souza Pietra, Renata Celi Carvalho |
collection | PubMed |
description | 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 20(th) 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) IC(50) 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 IC(50) 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. |
format | Online Article Text |
id | pubmed-3544846 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-35448462013-01-22 Triphenylmethane Derivatives Have High In Vitro and In Vivo Activity against the Main Causative Agents of Cutaneous Leishmaniasis de Souza Pietra, Renata Celi Carvalho Rodrigues, Lucas Fonseca Teixeira, Eliane Fried, Levi Lefkove, Benjamin Rabello, Ana Arbiser, Jack Ferreira, Lucas Antônio Miranda Fernandes, Ana Paula PLoS One Research Article 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 20(th) 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) IC(50) 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 IC(50) 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. Public Library of Science 2013-01-14 /pmc/articles/PMC3544846/ /pubmed/23341885 http://dx.doi.org/10.1371/journal.pone.0051864 Text en © 2013 Souza Pietra et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article de Souza Pietra, Renata Celi Carvalho Rodrigues, Lucas Fonseca Teixeira, Eliane Fried, Levi Lefkove, Benjamin Rabello, Ana Arbiser, Jack Ferreira, Lucas Antônio Miranda Fernandes, Ana Paula Triphenylmethane Derivatives Have High In Vitro and In Vivo Activity against the Main Causative Agents of Cutaneous Leishmaniasis |
title | Triphenylmethane Derivatives Have High In Vitro and In Vivo Activity against the Main Causative Agents of Cutaneous Leishmaniasis |
title_full | Triphenylmethane Derivatives Have High In Vitro and In Vivo Activity against the Main Causative Agents of Cutaneous Leishmaniasis |
title_fullStr | Triphenylmethane Derivatives Have High In Vitro and In Vivo Activity against the Main Causative Agents of Cutaneous Leishmaniasis |
title_full_unstemmed | Triphenylmethane Derivatives Have High In Vitro and In Vivo Activity against the Main Causative Agents of Cutaneous Leishmaniasis |
title_short | Triphenylmethane Derivatives Have High In Vitro and In Vivo Activity against the Main Causative Agents of Cutaneous Leishmaniasis |
title_sort | triphenylmethane derivatives have high in vitro and in vivo activity against the main causative agents of cutaneous leishmaniasis |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3544846/ https://www.ncbi.nlm.nih.gov/pubmed/23341885 http://dx.doi.org/10.1371/journal.pone.0051864 |
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