Untargeted LC-MS metabolomic studies of Asteraceae species to discover inhibitors of Leishmania major dihydroorotate dehydrogenase.
Autor: | Chibli LA; AsterBioChem Research Team, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Av. do Café s/n, Ribeirão Preto, SP, 14040-903, Brazil., Rosa AL; AsterBioChem Research Team, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Av. do Café s/n, Ribeirão Preto, SP, 14040-903, Brazil., Nonato MC; Laboratory of Protein Crystallography, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Av. do Café s/n, Ribeirão Preto, SP, 14040-903, Brazil., Da Costa FB; AsterBioChem Research Team, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Av. do Café s/n, Ribeirão Preto, SP, 14040-903, Brazil. febcosta@fcfrp.usp.br. |
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Jazyk: | angličtina |
Zdroj: | Metabolomics : Official journal of the Metabolomic Society [Metabolomics] 2019 Apr 04; Vol. 15 (4), pp. 59. Date of Electronic Publication: 2019 Apr 04. |
DOI: | 10.1007/s11306-019-1520-7 |
Abstrakt: | Introduction: Interesting data about the family Asteraceae as a new source of Leishmania major dihydroorotate dehydrogenase (LmDHODH) inhibitors are presented. This key macromolecular target for parasites causing neglected diseases catalyzes the fourth reaction of the de novo pyrimidine biosynthetic pathway, which takes part in major cell functions, including DNA and RNA biosynthesis. Objectives: We aimed to (1) determine LmDHODH inhibitor candidates, revealing the type of chemistry underlying such bioactivity, and (2) predict the inhibitory potential of extracts from new untested plant species, classifying them as active or inactive based on their LC-MS based metabolic fingerprints. Methods: Extracts from 150 species were screened for the inhibition of LmDHODH, and untargeted UHPLC-(ESI)-HRMS metabolomic studies were carried out in combination with in silico approaches. Results: The IC Conclusion: Our approach was validated for (1) the discovery of LmDHODH inhibitors or interesting starting points for the optimization of new leishmanicides from Asteraceae species and (2) the prediction of extracts from untested species, classifying them as active or inactive. |
Databáze: | MEDLINE |
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