New insights into the mechanistic action of methyldehydrodieugenol B towards Leishmania (L.) infantum via a multiplatform based untargeted metabolomics approach

New insights into the mechanistic action of methyldehydrodieugenol B towards Leishmania (L.) infantum via a multiplatform based untargeted metabolomics approach

Author Baptista Canuto, Gisele Andre Google Scholar
Dorr, Fabiane Google Scholar
Ghilardi Lago, Joao Henrique Autor UNIFESP Google Scholar
Tempone, Andre Gustavo Google Scholar
Pinto, Ernani Google Scholar
Pimenta, Daniel Carvalho Google Scholar
Simon Farah, Joao Pedro Google Scholar
Manso Alves, Maria Julia Google Scholar
Maggi Tavares, Marina Franco Google Scholar
Abstract Introduction Leishmaniasis is a parasitic neglected disease affecting millions of people worldwide. Clinical practice resorts to long and costly treatments with a therapeutic arsenal limited to highly toxic drugs, often associated to adverse side effects. Additionally, resistant strains are reported to be increasing. Aim In this work, the mechanistic action of a drug candidate (methydehydrodieugenol B), isolated from twigs of Nectandra leucantha, towards Leishmania infantum was studied by a global metabolomics approach using GC-MS and RPLC-MS platforms. Method L. infantum promastigotes were grown in culture medium for 72 h and treated with methydehydrodieugenol B at 58.18 mu g. mL(-1) concentration

after 48 h treatment, enzyme activity was quenched, cells washed and frozen until analysis. For GC-MS analysis (Fiehn's method), 1: 1 methanol: water extracts were prepared and derivatized with O-methoxyamine in pyridine at room temperature for 90 min, followed by silylation with BSTFA/1% TMCS at 40 degrees C for 30 min. Pure methanolic extracts were also prepared and analyzed directly by RPLC-MS with a acetonitrile/water mobile phase acidulated with formic acid and gradient elution. Result Several amino acids, fatty acids, carbohydrates, and glycerolipids were found as discriminant metabolites, mostly decreased in treated samples. Due to the complexity of the parasite metabolism and the great diversity of altered metabolites, a multi-target mechanism was assigned to the drug candidate, where changes in the cell energy sources and in the lipid composition of the parasite plasma membrane were prominent. Conclusion These results contributed to elucidate the broad action of methyldehydrodieugenol B against Leishmania, paving the way in the search of novel alternative therapies.
Keywords Metabolomics
Leishmania
Neglected diseases
Neolignan
Methyldehydrodieugenol B
Natural products
xmlui.dri2xhtml.METS-1.0.item-coverage New York
Language English
Sponsor Sao Paulo Research Foundation
FAPESP
Grant number FAPESP: 2012/04601-6
FAPESP: 2012/18756-1
FAPESP: 2012/07361-6
FAPESP: 2014/25494-9
FAPESP: 2015/50075-2
Date 2017
Published in Metabolomics. New York, v. 13, n. 5, p. -, 2017.
ISSN 1573-3882 (Sherpa/Romeo, impact factor)
Publisher Springer
Extent -
Origin http://dx.doi.org/10.1007/s11306-017-1193-z
Access rights Closed access
Type Article
Web of Science ID WOS:000399681400011
URI https://repositorio.unifesp.br/handle/11600/54691

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