Design, synthesis and biological evaluation of N-oxide derivatives with potent in vivo antileishmanial activity.

Leishmaniasis is a neglected disease that affects 12 million people living mainly in developing countries. Herein, 24 new N-oxide-containing compounds were synthesized followed by in vitro and in vivo evaluation of their antileishmanial activity. Compound 4f, a furoxan derivative, was particularly r...

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Autores principales:	Leandro da Costa Clementino, Guilherme Felipe Santos Fernandes, Igor Muccilo Prokopczyk, Wilquer Castro Laurindo, Danyelle Toyama, Bruno Pereira Motta, Amanda Martins Baviera, Flávio Henrique-Silva, Jean Leandro Dos Santos, Marcia A S Graminha
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/518d903179ec47c3a56720c797f90773
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spelling	oai:doaj.org-article:518d903179ec47c3a56720c797f907732021-12-02T20:04:36ZDesign, synthesis and biological evaluation of N-oxide derivatives with potent in vivo antileishmanial activity.1932-620310.1371/journal.pone.0259008https://doaj.org/article/518d903179ec47c3a56720c797f907732021-01-01T00:00:00Zhttps://doi.org/10.1371/journal.pone.0259008https://doaj.org/toc/1932-6203Leishmaniasis is a neglected disease that affects 12 million people living mainly in developing countries. Herein, 24 new N-oxide-containing compounds were synthesized followed by in vitro and in vivo evaluation of their antileishmanial activity. Compound 4f, a furoxan derivative, was particularly remarkable in this regard, with EC50 value of 3.6 μM against L. infantum amastigote forms and CC50 value superior to 500 μM against murine peritoneal macrophages. In vitro studies suggested that 4f may act by a dual effect, by releasing nitric oxide after biotransformation and by inhibiting cysteine protease CPB (IC50: 4.5 μM). In vivo studies using an acute model of infection showed that compound 4f at 7.7 mg/Kg reduced ~90% of parasite burden in the liver and spleen of L. infantum-infected BALB/c mice. Altogether, these outcomes highlight furoxan 4f as a promising compound for further evaluation as an antileishmanial agent.Leandro da Costa ClementinoGuilherme Felipe Santos FernandesIgor Muccilo ProkopczykWilquer Castro LaurindoDanyelle ToyamaBruno Pereira MottaAmanda Martins BavieraFlávio Henrique-SilvaJean Leandro Dos SantosMarcia A S GraminhaPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 16, Iss 11, p e0259008 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Leandro da Costa Clementino Guilherme Felipe Santos Fernandes Igor Muccilo Prokopczyk Wilquer Castro Laurindo Danyelle Toyama Bruno Pereira Motta Amanda Martins Baviera Flávio Henrique-Silva Jean Leandro Dos Santos Marcia A S Graminha Design, synthesis and biological evaluation of N-oxide derivatives with potent in vivo antileishmanial activity.
description	Leishmaniasis is a neglected disease that affects 12 million people living mainly in developing countries. Herein, 24 new N-oxide-containing compounds were synthesized followed by in vitro and in vivo evaluation of their antileishmanial activity. Compound 4f, a furoxan derivative, was particularly remarkable in this regard, with EC50 value of 3.6 μM against L. infantum amastigote forms and CC50 value superior to 500 μM against murine peritoneal macrophages. In vitro studies suggested that 4f may act by a dual effect, by releasing nitric oxide after biotransformation and by inhibiting cysteine protease CPB (IC50: 4.5 μM). In vivo studies using an acute model of infection showed that compound 4f at 7.7 mg/Kg reduced ~90% of parasite burden in the liver and spleen of L. infantum-infected BALB/c mice. Altogether, these outcomes highlight furoxan 4f as a promising compound for further evaluation as an antileishmanial agent.
format	article
author	Leandro da Costa Clementino Guilherme Felipe Santos Fernandes Igor Muccilo Prokopczyk Wilquer Castro Laurindo Danyelle Toyama Bruno Pereira Motta Amanda Martins Baviera Flávio Henrique-Silva Jean Leandro Dos Santos Marcia A S Graminha
author_facet	Leandro da Costa Clementino Guilherme Felipe Santos Fernandes Igor Muccilo Prokopczyk Wilquer Castro Laurindo Danyelle Toyama Bruno Pereira Motta Amanda Martins Baviera Flávio Henrique-Silva Jean Leandro Dos Santos Marcia A S Graminha
author_sort	Leandro da Costa Clementino
title	Design, synthesis and biological evaluation of N-oxide derivatives with potent in vivo antileishmanial activity.
title_short	Design, synthesis and biological evaluation of N-oxide derivatives with potent in vivo antileishmanial activity.
title_full	Design, synthesis and biological evaluation of N-oxide derivatives with potent in vivo antileishmanial activity.
title_fullStr	Design, synthesis and biological evaluation of N-oxide derivatives with potent in vivo antileishmanial activity.
title_full_unstemmed	Design, synthesis and biological evaluation of N-oxide derivatives with potent in vivo antileishmanial activity.
title_sort	design, synthesis and biological evaluation of n-oxide derivatives with potent in vivo antileishmanial activity.
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/518d903179ec47c3a56720c797f90773
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Design, synthesis and biological evaluation of N-oxide derivatives with potent in vivo antileishmanial activity.

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