Loganiaceae; Strychnos; malaria; antiplasmodial; mass spectrometry; metabolomics; chemoinformatics; molecular networking
Abstract :
[en] Malaria, a disease known for thousands of years and caused by parasites of the Plasmodium genus, continues to cause many deaths throughout the world today, particularly due to the emergence of parasite resistance to the current therapeutic arsenal. Plants of the Strychnos genus, remarkable due to their multiple traditional uses as well as their alkaloid content, are promising candidates to develop new antimalarial treatments. Indeed, previous research on this plant group has shown promising (≤ 5 µg/ml) or good (between 5 and 15 µg/ml) antiplasmodial activities. Using the chloroquine-sensitive strain of Plasmodium falciparum (3D7), and artemisinin as positive control, a screening of antiplasmodial activities from 43 crude methanolic extracts from 28 species of the Strychnos genus was carried out in three independent assays. A total of 12 extracts had good (6 extracts) or promising (6 extracts) antiplasmodial activities. These results allowed both to confirm known activities but also to detect new ones. These extracts were then analyzed by HPLC-ESI(+)-Q/TOF, and the processed MS/MS data allowed to generate a molecular network in which the antiplasmodial activities were implemented as metadata. The exploration of the molecular network revealed the presence of alkaloids still unknown, and potentially active against malaria, in particular alkaloids close to usambarensine and its derivatives. This study shows that the emergence of molecular networking offers new leads for identifications of alkaloids from the Strychnos genus. The presence of unknown alkaloids potentially active against malaria confirms all the interest to continue in studying the Strychnos genus. Bioassay- and mass-guided fractionations as well as various dereplication tools would allow to identify and characterize these interesting alkaloids further.
Disciplines :
Pharmacy, pharmacology & toxicology
Author, co-author :
Bonnet, Olivier ; Université de Liège - ULiège > Unités de recherche interfacultaires > Centre Interdisciplinaire de Recherche sur le Médicament (CIRM)
Beniddir, Mehdi A.; Université Paris-Saclay > Faculté de Pharmacie > Service de Pharmacognosie-Chimie des Substances Naturelles
Champy, Pierre; Université Paris-Saclay > Faculté de Pharmacie > Service de Pharmacognosie-Chimie des Substances Naturelles
Degotte, Gilles ; Université de Liège - ULiège > Unités de recherche interfacultaires > Centre Interdisciplinaire de Recherche sur le Médicament (CIRM)
Coelho Cristino Mamede, Lucia Cristina ; Université de Liège - ULiège > Unités de recherche interfacultaires > Centre Interdisciplinaire de Recherche sur le Médicament (CIRM)
Desdemoustier, Pauline ; Université de Liège - ULiège > Unités de recherche interfacultaires > Centre Interdisciplinaire de Recherche sur le Médicament (CIRM)
Ledoux, Allison ; Université de Liège - ULiège > Unités de recherche interfacultaires > Centre Interdisciplinaire de Recherche sur le Médicament (CIRM)
Tchinda, Alembert Tiabou; ULiège - Université de Liège > Unités de recherche interfacultaires > Centre Interdisciplinaire de Recherche sur le Médicament (CIRM)
Angenot, Luc ; Université de Liège - ULiège > Département de pharmacie
Frederich, Michel ; Université de Liège - ULiège > Unités de recherche interfacultaires > Centre Interdisciplinaire de Recherche sur le Médicament (CIRM)
Language :
English
Title :
Unveiling antiplasmodial alkaloids from a cumulative collection of Strychnos extracts by multi-informative molecular networks
Alternative titles :
[fr] Découverte d'alcaloïdes antiplasmodiques à partir d'une collection cumulative d'extraits de Strychnos par des réseaux moléculaires multi-informatifs
Allard P. Péresse T. Bisson J. Gindro K. Marcourt L. Pham V. C. et al. (2016). Integration of molecular networking and in-silico MS/MS fragmentation for natural products dereplication. Anal. Chem. 88 (6), 3317–3323. 10.1021/acs.analchem.5b04804
Angenot L. (1971). De l’existence en Afrique Centrale d’un poison de flèche curarisant, issu du Strychnos usambarensis. Ann. Pharm. Fr. 29 (5-6), 353–364.
Beniddir M. A. Kang K. B. Genta-Jouve G. Huber F. Rogers S. Van Der Hooft J. J. J. (2021). Advances in decomposing complex metabolite mixtures using substructure- and network-based computational metabolomics approaches. Nat. Prod. Rep. 38 (11), 1967–1993. 10.1039/D1NP00023C
Bisset N. G. (1970). The African species of Strychnos. I. The ethnobotany. Lloydia 33 (2), 201–243.
Bisset N. G. (1974). The Asian species of Strychnos. Part III. The ethnobotany. Lloydia 37 (1), 62–107.
Bruguière A. Derbré S. Dietsch J. Leguy J. Rahier V. Pottier Q. et al. (2020). MixONat, a software for the dereplication of mixtures based on 13C NMR spectroscopy. Anal. Chem. 92 (13), 8793–8801. 10.1021/acs.analchem.0c00193
Chambers M. C. Maclean B. Burke R. Amodei D. Ruderman D. L. Neumann S. et al. (2012). A cross-platform toolkit for mass spectrometry and proteomics. Nat. Biotechnol. 30 (10), 918–920. 10.1038/nbt.2377
Cox F. E. G. (2010). History of the discovery of the malaria parasites and their vectors. Parasit. Vectors 3 (5), 5–9. 10.1186/1756-3305-3-5
Dery V. Duah N. O. Torgby R. A. Matrevi S. A. Anto F. Quashie N. B. (2015). An improved SYBR Green 1 based fluorescence method for the routine monitoring of Plasmodium falciparum resistance to anti malarial drugs. Malar. J. 14, 481–486. 10.1186/s12936-015-1011-x
Dictionary of Natural Products (2022). 31.1. Available at: https://dnp.chemnetbase.com/faces/chemical/ChemicalSearch.xhtml (Accessed June 10, 2022).
Djoumbou Feunang Y. Eisner R. Knox C. Chepelev L. Hastings J. Owen G. et al. (2016). ClassyFire: Automated chemical classification with A comprehensive, computable taxonomy. J. Cheminform. 8, 61. 10.1186/s13321-016-0174-y
Dr. Duke's, Phytochemical and Ethnobotanical Databases (2021). Strychnos L. Available at: https://phytochem.nal.usda.gov/phytochem/search/list (Accessed May 18, 2022).
Egan J. M. van Santen A. Liu D. Y. Linington R. G. (2021). Development of an NMR-based platform for the direct structural annotation of complex natural products mixtures. J. Nat. Prod. 84 (4), 1044–1055. 10.1021/acs.jnatprod.0c01076
Eloff J. N. (1999). It is possible to use herbarium specimens to screen for antibacterial components in some plants. J. Ethnopharmacol. 67 (3), 355–360. 10.1016/S0378-8741(99)00053-7
Ernst M. Kang K. B. Caraballo-Rodríguez A. M. Nothias L. Wandy J. Chen C. et al. (2019). MolNetEnhancer: Enhanced molecular networks by integrating metabolome mining and annotation tools. Metabolites 9, E144. 10.3390/metabo9070144
Fentahun S. Makonnen E. Awas T. Giday M. (2017). In vivo antimalarial activity of crude extracts and solvent fractions of leaves of Strychnos mitis in Plasmodium berghei infected mice. BMC Complement. Altern. Med. 17 (1), 13–12. 10.1186/s12906-016-1529-7
Fox Ramos A. E. Evanno L. Poupon E. Champy P. Beniddir M. A. (2019a). Natural products targeting strategies involving molecular networking: Different manners, one goal. Nat. Prod. Rep. 36 (7), 960–980. 10.1039/c9np00006b
Fox Ramos A. E. Le Pogam P. Fox Alcover C. Otogo N’Nang E. Cauchie G. Hazni H. et al. (2019b). Collected mass spectrometry data on monoterpene indole alkaloids from natural product chemistry research. Sci. Data 6, 15. 10.1038/s41597-019-0028-3
Frédérich M. Tits M. Angenot L. (1998). Qualitative and quantitative evaluation of bisindole usambarane alkaloids in Strychnos usambarensis roots by high performance liquid chromatography-diode-array. Phytochem. Anal. 9 (2), 63–66. 10.1002/(SICI)1099-1565(199803/04)9:2<63::AID-PCA388>3.0.CO;2-9
Frédérich M. Hayette M. P. Tits M. De Mol P. Angenot L. (1999). In vitro activities of Strychnos alkaloids and extracts against Plasmodium falciparum. Antimicrob. Agents Chemother. 43 (9), 2328–2331. 10.1128/aac.43.9.2328
Frederich M. De Pauw M.-C. Llabres G. Tits M. Hayette M. P. Brandt V. et al. (2000). New antimalarial and cytotoxic sungucine derivatives from Strychnos icaja roots. Planta Med. 66 (3), 262–269. 10.1055/s-2000-8559
Frederich M. De Pauw M.-C. Prosperi C. Tits M. Brandt V. Penelle J. et al. (2001). Strychnogucines A and B, two new antiplasmodial bisindole alkaloids from Strychnos icaja. J. Nat. Prod. 64 (1), 12–16. 10.1021/np000285t
Frédérich M. Jacquier M. J. Thépenier P. De Mol P. Tits M. Philippe G. et al. (2002). Antiplasmodial activity of alkaloids from various Strychnos species. J. Nat. Prod. 65 (10), 1381–1386. 10.1021/np020070e
Frédérich M. Tits M. Angenot L. (2003). Indole alkaloids from Strychnos species and their antiplasmodial and cytotoxic activities. Khimiya Prir. Soedin. 39 (6), 425–429. 10.1021/np020070e
Harborne J. B. (2012). Phytochemical methods: A guide to modern techniques of plant analysis. third ed., 4. London: Chapman & Hall.
Jansen O. Tits M. Angenot L. Nicolas J.-P. De Mol P. Nikiema J.-B. et al. (2012). Anti-plasmodial activity of Dicoma tomentosa (Asteraceae) and identification of urospermal A-15-O-acetate as the main active compound. Malar. J. 11, 289. 10.1186/1475-2875-11-289
Krukoff B. A. (1972). American species of Strychnos. Lloydia 35 (2), 193–271. 10.5962/bhl.part.16789
Ledoux A. St-Gelais A. Cieckiewicz E. Jansen O. Bordignon A. Illien B. et al. (2017). Antimalarial activities of alkyl cyclohexenone derivatives isolated from the leaves of Poupartia borbonica. J. Nat. Prod. 80 (6), 1750–1757. 10.1021/acs.jnatprod.6b01019
Myers O. D. Sumner S. J. Li S. Barnes S. Du X. (2017). 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. 89 (17), 8696–8703. 10.1021/acs.analchem.7b00947
Nothias L. F. Nothias-Esposito M. Da Silva R. Wang M. Protsyuk I. Zhang Z. et al. (2018). Bioactivity-based molecular networking for the discovery of drug leads in natural product bioassay-guided fractionation. J. Nat. Prod. 81 (4), 758–767. 10.1021/acs.jnatprod.7b00737
Nothias L. F. Petras D. Schmid R. Dührkop K. Rainer J. Sarvepalli A. et al. (2020). Feature-based molecular networking in the GNPS analysis environment. Nat. Methods 17 (9), 905–908. 10.1038/s41592-020-0933-6
Philippe G. De Mol P. Zèches-Hanrot M. Nuzillard J.-M. Tits M. Angenot L. et al. (2002). Indolomonoterpenic alkaloids from Strychnos icaja roots. Phytochemistry 62 (4), 623–629. 10.1016/S0031-9422(02)00612-X
Philippe G. Angenot L. Tits M. Frédérich M. (2004). About the toxicity of some Strychnos species and their alkaloids. Toxicon 44 (4), 405–416. 10.1016/j.toxicon.2004.05.006
Philippe G. Angenot L. De Mol P. Goffin E. Hayette M. P. Tits M. et al. (2005). In vitro screening of some Strychnos species for antiplasmodial activity. J. Ethnopharmacol. 97 (3), 535–539. 10.1016/j.jep.2004.12.011
Philippe G. De Mol P. Angenot L. Tits M. Frédérich M. (2007). In vivo antimalarial activity of isosungucine, an indolomonoterpenic alkaloid from Strychnos icaja. Planta Med. 73 (5), 478–479. 10.1055/s-2007-967174
Phillipson J. D. (1982). Chemical investigations of herbarium material for alkaloids. Phytochemistry 2110, 2441–2456. 10.1016/0031-9422(82)85239-4
Pluskal T. Castillo S. Villar-Briones A. Orešič M. (2010). MZmine 2: Modular framework for processing, visualizing, and analyzing mass spectrometry-based molecular profile data. BMC Bioinform. 11, 395. 10.1186/1471-2105-11-395
Setubal R. B. Frasier C. L. Molina J. Torke B. M. Forzza R. C. Struwe L. (2021). A toxic story; phylogeny and classification of Strychnos L. (Loganiaceae). Syst. Bot. 46 (3), 639–655. 10.1600/036364421X16312067913444
Soto-Sobenis A. Castillo B. Delgado A. González A. Montenegro R. (2001). Alkaloid screening of herbarium samples of rubiaceae from Panama. Pharm. Biol. 39 (3), 161–169. 10.1076/phbi.39.3.161.5925
Tchinda A. T. Ngono A. R. N. Tamze V. Jonville M. C. Cao M. Angenot L. et al. (2012). Antiplasmodial alkaloids from the stem bark of Strychnos malacoclados. Planta Med. 78 (4), 377–382. 10.1055/s-0031-1280473
Tchinda A. T. Jansen O. Nyemb J. N. Tits M. Dive G. Angenot L. et al. (2014). Strychnobaillonine, an unsymmetrical bisindole alkaloid with an unprecedented skeleton from Strychnos icaja roots. J. Nat. Prod. 77 (4), 1078–1082. 10.1021/np400908u
Trager W. Jensen J. B. (1976). Human malaria parasites in continuous culture. Science 1934254, 673–675. 10.1126/science.781840
Wandy J. Zhu Y. Van Der Hooft J. J. J. Daly R. Barrett M. P. Rogers S. (2018). Ms2lda.org: Web-based topic modelling for substructure discovery in mass spectrometry. Bioinformatics 34 (2), 317–318. doi: 10.1093/bioinformatics/btx582.
Wang M. Carver J. J. Phelan V. V. Sanchez L. M. Garg N. Peng Y. et al. (2016). Sharing and community curation of mass spectrometry data with global natural products social molecular networking. Nat. Biotechnol. 34 (8), 828–837. 10.1038/nbt.3597
World Flora Online (2022). Strychnos L. Available at: http://www.worldfloraonline.org/taxon/wfo-4000036956 (Accessed May 1815, 2022).
World Health Organization (2021a). Global malaria programme. Available at: https://www.who.int/teams/global-malaria-programme/prevention/vector-control (Accessed May 18, 2022).
World Health Organization (2021b). World malaria report. Available at: https://www.who.int/publications/i/item/9789240040496 (Accessed May 18, 2022).
World Health Organization (2022). Guidelines for malaria. Available at: https://app.magicapp.org/#/guideline/6236 (Accessed May 18, 2022).
Wright C. W. Allen D. Cai Y. Chen Z. Phillipson J. D. Kirby G. C. et al. (1994). Selective antiprotozoal activity of some Strychnos alkaloids. Phytother. Res. 8 (3), 149–152. 10.1002/ptr.2650080306
Wright C. W. Phillipson J. D. Awe S. O. Kirby G. C. Warhurst D. C. Quetin-Leclercq J. et al. (1996). Antimalarial activity of cryptolepine and some other anhydronium bases. Phytother. Res. 104, 361–363. 10.1002/(SICI)1099-1573(199606)10:4<361::AID-PTR845>3.0.CO;2-N
Yang J. Y. Sanchez L. M. Rath C. M. Liu X. Boudreau P. D. Bruns N. et al. (2013). Molecular networking as a dereplication strategy. J. Nat. Prod. 76 (9), 1686–1699. 10.1021/np400413s
Yilmaz A. Nyberg N. T. Jaroszewski J. W. (2012). Extraction of alkaloids for NMR-based profiling: Exploratory analysis of an archaic cinchona bark collection. Planta Med. 78 (17), 1885–1890. 10.1055/s-0032-1315396