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- Title
Design, synthesis and biological evaluation of N-oxide derivatives with potent in vivo antileishmanial activity.
- Authors
Clementino, Leandro da Costa; Fernandes, Guilherme Felipe Santos; Prokopczyk, Igor Muccilo; Laurindo, Wilquer Castro; Toyama, Danyelle; Motta, Bruno Pereira; Baviera, Amanda Martins; Henrique-Silva, Flávio; Santos, Jean Leandro dos; Graminha, Marcia A. S.
- Abstract
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.
- Subjects
BIOSYNTHESIS; NEGLECTED diseases; PERITONEAL macrophages; SPLEEN; BIOCONVERSION; NITRIC oxide
- Publication
PLoS ONE, 2021, Vol 16, Issue 11, p1
- ISSN
1932-6203
- Publication type
Article
- DOI
10.1371/journal.pone.0259008