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Planta Med 2017; 83(07): 636-646
DOI: 10.1055/s-0042-118712
Natural Product Chemistry and Analytical Studies
Original Papers
Georg Thieme Verlag KG Stuttgart · New York

Dereplication of Flavonoid Glycoconjugates from Adenocalymma imperatoris-maximilianii by Untargeted Tandem Mass Spectrometry-Based Molecular Networking

Gibson Gomes de Oliveira   *
1   Departamento de Física e Química, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP, Brazil
,
Fausto Carnevale Neto   *
1   Departamento de Física e Química, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP, Brazil
,
Daniel Pecoraro Demarque
1   Departamento de Física e Química, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP, Brazil
,
José Antônio de Sousa Pereira-Junior
2   Centro de Ciências da Saúde, Faculdade Escritor Osman da Costa Lins, Vitória de Santo Antão, PE, Brazil
,
Rômulo César Sampaio Peixoto Filho
3   Departamento de Antibióticos, Universidade Federal de Pernambuco, Recife, PE, Brazil
,
Sebastião José de Melo
3   Departamento de Antibióticos, Universidade Federal de Pernambuco, Recife, PE, Brazil
,
Jackson Roberto Guedes da Silva Almeida
4   Núcleo de Estudos e Pesquisas de Plantas Medicinais, Universidade Federal do Vale do São Francisco, Petrolina, PE, Brazil
,
João Luiz Callegari Lopes
1   Departamento de Física e Química, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP, Brazil
,
Norberto Peporine Lopes
1   Departamento de Física e Química, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP, Brazil
› Author Affiliations
Further Information

Publication History

received 03 August 2016
revised 21 September 2016

accepted 01 October 2016

Publication Date:
02 November 2016 (online)

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Abstract

The interpretation of large datasets acquired using high performance liquid chromatography coupled with tandem mass spectrometry represents one of the major challenges in natural products research. Here we propose the use of molecular networking to rapid identify the known secondary metabolites from untargeted MS/MS analysis of Adenocalymma imperatoris-maximilianii plant extracts. The leaves, stems and roots of A. imperatoris-maximilianii were extracted using different solvents according to Snyder selectivity triangle. The samples were analyzed by HPLC coupled with ion trap mass spectrometer in a collision-induced dissociation MS/MS configuration in both positive and negative electrospray ionization modes. Molecular networking simultaneously organized the spectra by cosine similarity. The chemical identification was performed based on the systematic study of the main fragmentation pathways observed for the resulting network. The untargeted tandem mass spectrometry-based molecular networking allowed for the identification of 63 metabolites, mainly mono-, di- and tri-, C- and/or O-glycosyl flavones. Molecular networking was capable not only to dereplicate known flavonoids, but also to point out related prenyl derivatives, described for the first time in Adenocalymma species. The gas-phase reaction route to form the characteristic [M-H2O-(30/60/90)]+ fragments in C-glycosyl flavones was suggested as sequential sugar ring opening followed by retro-aldol elimination involving aldose-ketose isomerization. The use of molecular networking with LC–CID-MS/MS assisted the identification of various isomeric and isobaric flavonoid glycoconjugates by establishing clusters according to the fragmentation similarities. Additionally, the proposed cross-ring sugar cleavages can contribute to the identification of C-glycosides by MS/MS analysis.

Key words

Adenocalymma imperatoris-maximilianii - Bignoniaceae - molecular networking - flavonoid glycosides - aldose-ketose isomerization - retro-aldol

* Co-first authors.


Supporting Information

The MS and MS/MS data of compounds 1–63 and the HRMS and NMR spectra of compound 46 are available as Supporting Information.

 

  • References

  • 1 Nielsen KF, Mansson M, Rank C, Frisvad JC, Larsen TO. Dereplication of microbial natural products by LC-DAD-TOFMS. J Nat Prod 2011; 74: 2338-2348
    CrossrefPubMedSearch in Google Scholar
  • 2 Carnevale Neto F, Pilon AC, Selegato DM, Freire RT, Gu H, Raftery D, Lopes NP, Castro-Gamboa I. Dereplication of natural products using GC-TOF mass spectrometry: improved metabolite identification by spectral deconvolution ratio analysis. Front Mol Biosci 2016; 3: 1-13
    PubMedSearch in Google Scholar
  • 3 Dinan L. Dereplication and partial Identification of Compounds. In: Sarker SD, Latif Z, Gray AI. eds. Natural Products Isolation. 2nd ed. Totowa, NJ: Humana Press Inc.; 2005: 297-321
    Search in Google Scholar
  • 4 Smith CA, OʼMaille G, Want EJ, Qin C, Trauger SA, Brandon TR, Custodio DE, Abagyan R, Siuzdak G. METLIN: a metabolite mass spectral database. Ther Drug Monit 2005; 27: 747-751
    CrossrefPubMedSearch in Google Scholar
  • 5 Blunt JW, Munro MH. Dictionary of marine natural Products. With CD-ROM. Boca Ratom, FL: CRC Press; 2007
    Search in Google Scholar
  • 6 Lang G, Mayhudin NA, Mitova MI, Sun L, van der Sar S, Blunt JW, Cole ALJ, Ellis G, Laatsch H, Munro MHG. Evolving trends in the dereplication of natural product extracts: New methodology for rapid, small-scale investigation of natural product extracts. J Nat Prod 2008; 71: 1595-1599
    CrossrefPubMedSearch in Google Scholar
  • 7 Ernst M, Silva DB, Silva RR, Vêncio RZ, Lopes NP. Mass spectrometry in plant metabolomics strategies: from analytical platforms to data acquisition and processing. Nat Prod Rep 2014; 31: 784-806
    CrossrefPubMedSearch in Google Scholar
  • 8 Wolfender J-L, Rudaz S, Hae Choi Y, Kyong Kim H. Plant metabolomics: from holistic data to relevant biomarkers. Current Med Chem 2013; 20: 1056-1090
    PubMedSearch in Google Scholar
  • 9 Carnevale Neto F, Siquitelli CD, Pilon AC, Silva DH, Bolzani VdS, Castro-Gamboa I. Dereplication of phenolic derivatives of Qualea grandiflora and Qualea cordata (Vochysiaceae) using liquid chromatography coupled with ESI-QToF-MS/MS. J Braz Chem Soc 2013; 24: 758-764
    PubMedSearch in Google Scholar
  • 10 Funari CS, Eugster PJ, Martel S, Carrupt P-A, Wolfender J-L, Silva DHS. High resolution ultra high pressure liquid chromatography-time-of-flight mass spectrometry dereplication strategy for the metabolite profiling of Brazilian Lippia species. J Chromatogr A 2012; 1259: 167-178
    CrossrefPubMedSearch in Google Scholar
  • 11 Pilon AC, Carneiro RL, Carnevale Neto F, da S Bolzani V, Castro-Gamboa I. Interval multivariate curve resolution in the dereplication of HPLC-DAD data from Jatropha gossypifolia . Phytochem Anal 2013; 24: 401-406
    CrossrefPubMedSearch in Google Scholar
  • 12 Yang JY, Sanchez LM, Rath CM, Liu X, Boudreau PD, Bruns N, Glukhov E, Wodtke A, de Felicio R, Fenner A. Molecular networking as a dereplication strategy. J Nat Prod 2013; 76: 1686-1699
    CrossrefPubMedSearch in Google Scholar
  • 13 Gu H, Gowda GN, Carnevale Neto F, Opp MR, Raftery D. RAMSY: Ratio analysis of mass spectrometry to improve compound identification. Anal Chem 2013; 85: 10771-10779
    CrossrefPubMedSearch in Google Scholar
  • 14 Allard P-M, Péresse T, Bisson J, Gindro K, Marcourt L, Pham VC, Roussi F, Litaudon M, Wolfender J-L. Integration of molecular networking and in-silico MS/MS fragmentation for natural products dereplication. Anal Chem 2016; 88: 3317-3323
    CrossrefPubMedSearch in Google Scholar
  • 15 Watrous J, Roach P, Alexandrov T, Heath BS, Yang JY, Kersten RD, van der Voort M, Pogliano K, Gross H, Raaijmakers JM. Mass spectral molecular networking of living microbial colonies. Proc Natl Acad Sci 2012; 109: E1743-E1752
    CrossrefPubMedSearch in Google Scholar
  • 16 Wang M, Carver JJ, Phelan VV, Sanchez LM, Garg N, Peng Y, Nguyen DD, Watrous J, Kapono CA, Luzzatto-Knaan T. Sharing and community curation of mass spectrometry data with global natural products social molecular networking. Nature Biotech 2016; 34: 828-837
    CrossrefPubMedSearch in Google Scholar
  • 17 Zoghbi MdGB, Oliveira J, Guilhon GMSP. The genus Mansoa (Bignoniaceae): a source of organosulfur compounds. Rev Bras Farmacogn 2009; 19: 795-804
    CrossrefPubMedSearch in Google Scholar
  • 18 Choudhury S, Datta S, Talukdar AD, Choudhury MD. Phytochemistry of the family Bignoniaceae – a review. Assam Univ J Sci Tech 2011; 7: 145-150
    PubMedSearch in Google Scholar
  • 19 Appa Rao M, Venkata Rao E. Flavonoids of the flowers of Adenocalymma alliaceum . Curr Sci 1980; 49: 468-469
    PubMedSearch in Google Scholar
  • 20 Zoghbi MdGB, Andrade EHA, Maia JGS. Volatile constituents from Adenocalymma alliaceum Miers and Petiveria alliacea L., two medicinal herbs of the Amazon. Flavour Frag J 2002; 17: 133-135
    CrossrefPubMedSearch in Google Scholar
  • 21 Cuyckens F, Claeys M. Mass spectrometry in the structural analysis of flavonoids. J Mass Spec 2004; 39: 1-15
    CrossrefPubMedSearch in Google Scholar
  • 22 Ferreres F, Llorach R, Gil-Izquierdo A. Characterization of the interglycosidic linkage in di-, tri-, tetra- and pentaglycosylated flavonoids and differentiation of positional isomers by liquid chromatography/electrospray ionization tandem mass spectrometry. J Mass Spec 2004; 39: 312-321
    CrossrefPubMedSearch in Google Scholar
  • 23 Gobbo-Neto L, Lopes NP. Online identification of chlorogenic acids, sesquiterpene lactones, and flavonoids in the Brazilian arnica Lychnophora ericoides Mart. (Asteraceae) leaves by HPLC-DAD-MS and HPLC-DAD-MS/MS and a validated HPLC-DAD method for their simultaneous analysis. J Agric Food Chem 2008; 56: 1193-1204
    CrossrefPubMedSearch in Google Scholar
  • 24 Wolfender J-L, Waridel P, Ndjoko K, Hobby K, Major H, Hostettmann K. Evaluation of Q-TOF-MS/MS and multiple stage IT-MSn for the dereplication of flavonoids and related compounds in crude plant extracts. Analusis 2000; 28: 895-906
    CrossrefPubMedSearch in Google Scholar
  • 25 Cuyckens F, Claeys M. Determination of the glycosylation site in flavonoid mono-O-glycosides by collision-induced dissociation of electrospray-generated deprotonated and sodiated molecules. J Mass Spec 2005; 40: 364-372
    CrossrefPubMedSearch in Google Scholar
  • 26 Stobiecki M. Application of mass spectrometry for identification and structural studies of flavonoid glycosides. Phytochemistry 2000; 54: 237-256
    CrossrefPubMedSearch in Google Scholar
  • 27 Fridén ME, Sjöberg PJ. Strategies for differentiation of isobaric flavonoids using liquid chromatography coupled to electrospray ionization mass spectrometry. J Mass Spec 2014; 49: 646-663
    CrossrefPubMedSearch in Google Scholar
  • 28 Stobiecki M, Kachlicki P, Wojakowska A, Marczak Ł. Application of LC/MS systems to structural characterization of flavonoid glycoconjugates. Phytochem Lett 2015; 11: 358-367
    CrossrefPubMedSearch in Google Scholar
  • 29 Vukics V, Guttman A. Structural characterization of flavonoid glycosides by multi-stage mass spectrometry. Mass Spec Rev 2010; 29: 1-16
    PubMedSearch in Google Scholar
  • 30 Simons R, Vincken JP, Bakx EJ, Verbruggen MA, Gruppen H. A rapid screening method for prenylated flavonoids with ultra-high-performance liquid chromatography/electrospray ionisation mass spectrometry in licorice root extracts. Rapid Commun Mass Spec 2009; 23: 3083-3093
    CrossrefPubMedSearch in Google Scholar
  • 31 March RE, Lewars EG, Stadey CJ, Miao X-S, Zhao X, Metcalfe CD. A comparison of flavonoid glycosides by electrospray tandem mass spectrometry. Int J Mass Spec 2006; 248: 61-85
    CrossrefPubMedSearch in Google Scholar
  • 32 Waridel P, Wolfender J-L, Ndjoko K, Hobby KR, Major HJ, Hostettmann K. Evaluation of quadrupole time-of-flight tandem mass spectrometry and ion-trap multiple-stage mass spectrometry for the differentiation of C-glycosidic flavonoid isomers. J Chromatogr A 2001; 926: 29-41
    CrossrefPubMedSearch in Google Scholar
  • 33 Snyder L. Classification of the solvent properties of common liquids. J Chromat Sci 1978; 16: 223-234
    CrossrefPubMedSearch in Google Scholar
  • 34 Pilon AC, Carnevale Neto F, Freire RT, Cardoso P, Carneiro RL, Bolzani VDS, Castro-Gamboa I. Partial least squares model and design of experiments towards the analysis of the metabolome of Jatropha gossypifolia leaves: Extraction and chromatographic fingerprint optimization. J Sep Sci 2016; 39: 1023-1030
    CrossrefPubMedSearch in Google Scholar
  • 35 Demarque DP, Crotti AE, Vessecchi R, Lopes JL, Lopes NP. Fragmentation reactions using electrospray ionization mass spectrometry: an important tool for the structural elucidation and characterization of synthetic and natural products. Nat Prod Rep 2016; 33: 432-455
    CrossrefPubMedSearch in Google Scholar
  • 36 Cuyckens F, Ma Y, Pocsfalvi G, Claeys M. Tandem mass spectral strategies for the structural characterization of flavonoid glycosides. Analusis 2000; 28: 888-895
    CrossrefPubMedSearch in Google Scholar
  • 37 Pereira CA, Yariwake JH, McCullagh M. Distinction of the C-glycosylflavone isomer pairs orientin/isoorientin and vitexin/isovitexin using HPLC-MS exact mass measurement and in-source CID. Phytochem Anal 2005; 16: 295-301
    CrossrefPubMedSearch in Google Scholar
  • 38 Vukics V, Ringer T, Kery A, Bonn GK, Guttman A. Analysis of heartsease (Viola tricolor L.) flavonoid glycosides by micro-liquid chromatography coupled to multistage mass spectrometry. J Chromatogr A 2008; 1206: 11-20
    CrossrefPubMedSearch in Google Scholar
  • 39 Abad-García B, Garmón-Lobato S, Berrueta LA, Gallo B, Vicente F. A fragmentation study of dihydroquercetin using triple quadrupole mass spectrometry and its application for identification of dihydroflavonols in Citrus juices. Rapid Commun Mass Spec 2009; 23: 2785-2792
    CrossrefPubMedSearch in Google Scholar
  • 40 Gates PJ, Lopes NP. Characterisation of flavonoid aglycones by negative ion chip-based nanospray tandem mass spectrometry. Int J Anal Chem 2012; 2012: 259217
    PubMedSearch in Google Scholar
  • 41 Ma Y, Li Q, Van den Heuvel H, Claeys M. Characterization of flavone and flavonol aglycones by collision-induced dissociation tandem mass spectrometry. Rapid Commun Mass Spec 1997; 11: 1357-1364
    CrossrefPubMedSearch in Google Scholar
  • 42 Grayer RJ, Veitch NC, Kite GC, Paton AJ, Garnock-Jones PJ. Scutellarein 4′-methyl ether glycosides as taxonomic markers in Teucridium and Tripora (Lamiaceae, Ajugoideae). Phytochemistry 2002; 60: 727-731
    CrossrefPubMedSearch in Google Scholar
  • 43 Vessecchi R, Zocolo GJ, Gouvea DR, Huebner F, Cramer B, de Marchi MR, Humpf HU, Lopes NP. Re-examination of the anion derivatives of isoflavones by radical fragmentation in negative electrospray ionization tandem mass spectrometry: experimental and computational studies. Rapid Commun Mass Spec 2011; 25: 2020-2026
    CrossrefPubMedSearch in Google Scholar
  • 44 Rao AS. Root flavonoids. Bot Rev 1990; 56: 1-84
    CrossrefPubMedSearch in Google Scholar
  • 45 Da Rocha CQ, Queiroz EF, Meira CS, Moreira DRM, Soares MBP, Marcourt L, Vilegas W, Wolfender J-L. Dimeric flavonoids from Arrabidaea brachypoda and assessment of their anti-Trypanosoma cruzi activity. J Nat Prod 2014; 77: 1345-1350
    CrossrefPubMedSearch in Google Scholar
  • 46 Fournet A, Muñoz V. Natural products as trypanocidal, antileishmanial and antimalarial drugs. Curr Top Med Chem 2002; 2: 1215-1237
    CrossrefPubMedSearch in Google Scholar
  • 47 Gomes A, Fernandes E, Lima JL, Mira L, Corvo ML. Molecular mechanisms of anti-inflammatory activity mediated by flavonoids. Curr Med Chem 2008; 15: 1586-1605
    CrossrefPubMedSearch in Google Scholar
  • 48 Kessner D, Chambers M, Burke R, Agus D, Mallick P. ProteoWizard: open source software for rapid proteomics tools development. Bioinformatics 2008; 24: 2534-2536
    CrossrefPubMedSearch in Google Scholar
  • 49 Shannon P, Markiel A, Ozier O, Baliga NS, Wang JT, Ramage D, Amin N, Schwikowski B, Ideker T. Cytoscape: a software environment for integrated models of biomolecular interaction networks. Genome Res 2003; 13: 2498-2504
    CrossrefPubMedSearch in Google Scholar