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...

Descripción completa

Guardado en:

Detalles Bibliográficos
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/b5f6d88a45434c8e983019e31e61b2e6
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:b5f6d88a45434c8e983019e31e61b2e6
record_format	dspace
spelling	oai:doaj.org-article:b5f6d88a45434c8e983019e31e61b2e62021-11-11T06:44:22ZDesign, synthesis and biological evaluation of N-oxide derivatives with potent in vivo antileishmanial activity1932-6203https://doaj.org/article/b5f6d88a45434c8e983019e31e61b2e62021-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8559926/?tool=EBIhttps://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 (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/b5f6d88a45434c8e983019e31e61b2e6
work_keys_str_mv	AT leandrodacostaclementino designsynthesisandbiologicalevaluationofnoxidederivativeswithpotentinvivoantileishmanialactivity AT guilhermefelipesantosfernandes designsynthesisandbiologicalevaluationofnoxidederivativeswithpotentinvivoantileishmanialactivity AT igormucciloprokopczyk designsynthesisandbiologicalevaluationofnoxidederivativeswithpotentinvivoantileishmanialactivity AT wilquercastrolaurindo designsynthesisandbiologicalevaluationofnoxidederivativeswithpotentinvivoantileishmanialactivity AT danyelletoyama designsynthesisandbiologicalevaluationofnoxidederivativeswithpotentinvivoantileishmanialactivity AT brunopereiramotta designsynthesisandbiologicalevaluationofnoxidederivativeswithpotentinvivoantileishmanialactivity AT amandamartinsbaviera designsynthesisandbiologicalevaluationofnoxidederivativeswithpotentinvivoantileishmanialactivity AT flaviohenriquesilva designsynthesisandbiologicalevaluationofnoxidederivativeswithpotentinvivoantileishmanialactivity AT jeanleandrodossantos designsynthesisandbiologicalevaluationofnoxidederivativeswithpotentinvivoantileishmanialactivity AT marciaasgraminha designsynthesisandbiologicalevaluationofnoxidederivativeswithpotentinvivoantileishmanialactivity
_version_	1718439433286451200

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

Ejemplares similares