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DOI: 10.1055/a-1576-4351
Anticipate, Target and Characterize: MS²-anticipated C-glycosylflavones from Erythrococca anomala
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Abstract
We herein report on the first chemical assessment of Erythrococca anomala (Juss. ex Poir.) Prain (Euphorbiaceae), a genus that was – to the best of our knowledge – not studied yet from a phytochemical perspective. A molecular networking strategy was implemented to rapidly identify the known specialized metabolites from untargeted MS/MS analyses of E. anomala leaves ethanolic extract. This strategy allowed for the identification of diverse C-glycosyl flavones and a cursory examination of MS/MS spectra could extend the GNPS-provided annotation to pinpoint the structural novelty of further derivatives. The isolation of the sought-after structures could be streamlined based on MS-guidance and their structures, determined through extensive NMR analyses, displayed structural features in line with MS²-based predictions. Anticipating sharp structural features at an early stage of the dereplication process through a critical assessment of the tandem mass spectrometric landmarks was essential to embark on the isolation of the newly reported structures owing to the elevated number of flavonoid glycosides isomers thereof formerly known, which would have deterred us from isolating them without the support of additional tandem mass spectrometric information. The isolation of the main components of the ethanolic extract completed the currently provided chemical report on E. anomala, also resulting in the description of a new phenylethanoid derivative (3) and of a new orcinol-based dimer (4). Anomaloflavone (1) exhibit significant activities with minimal inhibitory concentration values of 25 µg/mL against Staphylococcus aureus and Mycobacterium smegmatis while failing to exert an antibacterial activity against Pseudomonas aeruginosa, while being devoid of cytotoxicity against SiHa cells.
Key words
natural products anticipation - molecular networking - flavones - Erythrococca anomala - Euphorbiaceae.Publikationsverlauf
Eingereicht: 02. Juni 2021
Eingereicht: 28. Juni 2021
Angenommen: 19. Juli 2021
Artikel online veröffentlicht:
29. Oktober 2021
© 2021. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial-License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).
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References
- 1 Webster GL. Euphorbiaceae. In: Kubitzki K, Editor. Flowering Plants Eudicots. Heidelberg: Springer-Verlag; 2014: 51-216
- 2 Burkill HM. The useful plants of west tropical Africa. Volume 2 : Families EI. Royal Botanic Garden Kew 1994; 636
- 3 Fox Ramos AE, Evanno L, Poupon E, Champy P, Beniddir MA. Natural products targeting strategies involving molecular networking: Different manners, one goal. Nat Prod Rep 2019; 36: 960-980
- 4 Fox Ramos AE, Pavesi C, Litaudon M, Dumontet V, Poupon E, Champy P. et al. CANPA: computer-assisted natural products anticipation. Anal Chem 2019; 91: 11247-11252
- 5 Allen F, Greiner R, Wishart D. Competitive fragmentation modeling of ESI-MS/MS spectra for putative metabolite identification. Metabolomics 2015; 11: 98-110
- 6 Beauxis Y, Genta-Jouve G. MetWork: a web server for natural products anticipation. Bioinformatics 2019; 35: 1795-1796
- 7 Turpin V, Beniddir MA, Genta-Jouve G, Skiredj A, Gallard J-F, Leblanc K. et al. In silico anticipation of metabolic pathways extended to organic chemistry reactions: a case study with caffeine alkaline hydrolysis and the origin of camellimidazoles. Chem Eur J 2020; 26: 12936-12940
- 8 Nothias L-F, Petras D, Schmid R, Dührkop K, Rainer J, Sarvepalli A. et al. Feature-based molecular networking in the GNPS analysis environment. Nat Methods 2020; 17: 905-908
- 9 Wang M, Carver JJ, Phelan VV, Sanchez LM, Garg N, Peng Y. et al. Sharing and community curation of mass spectrometry data with Global Natural Products Social Molecular Networking. Nat Biotechnol 2016; 34: 828-837
- 10 Rizk A-FM. The chemical constituents and economic plants of the Euphorbiaceae. Bot J Lin Soc 1987; 94: 293-326
- 11 Kuster RM, Mors WB, Wagner H. Orcinol glucosides from Phyllanthus klotzschianus. Fitoterapia. 1996; 67: 283-284
- 12 Cuyckens F, Claeys M. Mass spectrometry in the structural analysis of flavonoids. J Mass Spectrom 2004; 39: 1-15
- 13 Markham KR, Chari VM. Carbon-13 NMR Spectroscopy of Flavonoids. In: Harborne JB, Mabry TJ, Editors. The Flavonoids. Boston, MA: Springer US; 1982: 50
- 14 Pluskal T, Castillo S, Villar-Briones A, Orešič M. MZmine 2: modular framework for processing, visualizing, and analyzing mass spectrometry-based molecular profile data. BMC bioinformatics 2010; 11: 1-11
- 15 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
- 16 Pereira CAM, 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
- 17 Li QM, Claeys M. Characterization and differentiation of diglycosyl flavonoids by positive ion fast atom bombardment and tandem mass spectrometry. Biol Mass Spectrom 1994; 23: 406-416
- 18 Colombo R, Yariwake JH, McCullagh M. Study of C- and O-glycosylflavones in sugarcane extracts using liquid chromatography: exact mass measurement mass spectrometry. J Braz Chem Soc 2008; 19: 483-490
- 19 Kite GC, Porter EA, Denison FC, Grayer RJ, Veitch NC, Butler I. et al. Data-directed scan sequence for the general assignment of C-glycosylflavone O-glycosides in plant extracts by liquid chromatography-ion trap mass spectrometry. J Chromatogr A 2006; 1104: 123-131
- 20 Becchi M, Fraisse D. Fast atom bombardment and fast atom bombardment collision-activated dissociation/mass-analysed ion kinetic energy analysis of C-glycosidic flavonoids. Biomed Environ Mass Spectrom 1989; 18: 122-130
- 21 Qimin L, van den Heuvel H, Delorenzo O, Corthout J, Pieters LAC, Vlietinck AJ. et al. Mass spectral characterization of C-glycosidic flavonoids isolated from a medicinal plant (Passiflora incarnata). J Chromatogr B 1991; 562: 435-446
- 22 Wirasutisna KR, Gleye J, Moulis C, Stanislas E, Moretti C. Flavone C-Glycosides of Almeidea guyanensis. Phytochemistry 1986; 25: 558-559
- 23 DNP http://dnp.chemnetbase.com/ 2021
- 24 Nawwar MAM, Buddrus J, Bauer H. Dimeric phenolic constituents from the roots of Tamarix nilotica. Phytochemistry 1982; 21: 1755-1758
- 25 Fonseca SF, de Paiva Campello J, Barata LES, Rúveda EA. 13C NMR spectral analysis of lignans from Araucaria angustifolia. Phytochemistry 1978; 17: 499-502
- 26 Phommart S, Sutthivaiyakit P, Chimnoi N, Ruchirawat S, Sutthivaiyakit S. Constituents of the Leaves of Macaranga tanarius. J Nat Prod 2005; 68: 927-930
- 27 Choo CY, Sulong NY, Man F, Wong TW. Vitexin and isovitexin from the leaves of Ficus deltoidea with in-vivo α-glucosidase inhibition. J Ethnopharmacol 2012; 142: 776-781
- 28 Oelrichs P, Marshall JTB, Williams DH. 7-O-β-D-glucosyl-8-C-β-D-glucosyl-4′-O-methylapigenin. A new flavone from Trema aspera. J Chem Soc C 1968; 941-947
- 29 Marston A, Hostettmann K, Jacot-Guillarmod A. Contribution à la phytochimie du genre Gentiana, XIX. Identification de nouveaux C-glucosides flavoniques dans Gentiana pyrenaica L. Helv Chim Acta 1976; 59: 2596-2600
- 30 Lin M-T, Chen L-C, Chen C-K, Chen Liu KCS, Lee S-S. Chemical Constituents from Drypetes littoralis. J Nat Prod 2001; 64: 707-709
- 31 Agrawal PK. Carbon-13 NMR of flavonoids. London: Elsevier; 1989
- 32 Wawer I, Zielinska A. 13C CP/MAS NMR studies of flavonoids. Magn Reson Chem 2001; 39: 374-380
- 33 Xu K-J, Xu X-M, Deng W-L, Zhang L, Wang M-K, Ding L-S. Three new flavone C -glycosides from the aerial parts of Paraquilegia microphylla. J Asian Nat Prod Res 2011; 13: 409-416
- 34 Aquino R, Morelli S, Lauro MR, Abdo S, Saija A, Tomaino A. Phenolic Constituents and Antioxidant Activity of an Extract of Anthurium versicolor Leaves. J Nat Prod 2001; 64: 1019-1023
- 35 Markham KR, Whitehouse LA. Unique flavonoid glycosides from the new zealand white pine, Dacrycarpus dacrydioides. Phytochemistry 1984; 23: 1931-1936
- 36 Cheng Y, Schneider B, Oberthür C, Graf H, Adler S, Hamburger M. Flavone C-glycosides from Isatis tinctoria leaves. Heterocycles 2005; 65: 1655-1661
- 37 Lu Y, Yeap Foo L. Flavonoid and phenolic glycosides from Salvia officinalis. Phytochemistry 2000; 55: 263-267
- 38 Xie C, Veitch NC, Houghton PJ, Simmonds MSJ. Flavone C-Glycosides from Viola yedoensis Makino. Chem Pharm Bull 2003; 51: 1204-1207
- 39 Zhou G, Yan R, Wang X, Li S, Lin J, Liu J. et al. The overlooked rotational isomerism of C-glycosyl flavonoids. Phytochemistry Reviews 2019; 18: 443-461
- 40 Daglia M. Polyphenols as antimicrobial agents. Curr Opin Biotechnol 2012; 23: 174-181
- 41 Barbieri R, Coppo E, Marchese A, Daglia M, Sobarzo-Sánchez E, Nabavi SF. et al. Phytochemicals for human disease: An update on plant-derived compounds antibacterial activity. Microbiol Res 2017; 196: 44-68
- 42 Dwivedi P, Bendiak B, Clowers BH, Hill HH. Rapid resolution of carbohydrate isomers by electrospray ionization ambient pressure ion mobility spectrometry-time-of-flight mass spectrometry (ESI-APIMS-TOFMS). J Am Soc Mass Spectr 2007; 18: 1163-1175
- 43 Chambers MC, Maclean B, Burke R, Amodei D, Ruderman DL, Neumann S. et al. A cross-platform toolkit for mass spectrometry and proteomics. Nat Biotechnol 2012; 30: 918-920
- 44 Myers OD, Sumner SJ, Li S, Barnes S, Du X. One step forward for reducing false positive and false negative compound identifications from mass spectrometry metabolomics data: new algorithms for constructing extracted ion chromatograms and detecting chromatographic peaks. Anal Chem 2017; 89: 8696-8703
- 45 Shannon P, Markiel A, Ozier O, Baliga NS, Wang JT, Ramage D. et al. Cytoscape: A software environment for integrated models of biomolecular interaction networks. Genome Res 2003; 13: 2498-2504