The Antimalarial Potential of Three Ghanaian Medicinal Plants

Objective: Malaria is a major public health problem in Ghana and many indigenes, especially those in rural areas, resort to the use of medicinal plants to treat the disease. The plants: Persea americana Mill. (Lauraceae), Theobroma cacao L. (Malvaceae) and Tridax procumbens (L.) L. (Compositae) are used solely or in combination with other medicinal plants to manage malaria and its associated conditions. The leaves of the plants which are normally the main parts employed, were studied for their phytochemistry and antiplasmodial activity to establish their chemical profile and verify the antimalarial claim. Methods: Plant materials were subjected to basic phytochemical screening to identify the major secondary metabolites. The aqueous extracts were evaluated against chloroquine-sensitive 3D7 P. falciparum and chloroquine-resistant W2 P. falciparum strains, using the fluorescence-based SYBR® green I method to determine their antiplasmodial activity. Results: Basic phytochemical screening of the leaves revealed the presence of tannins, flavonoids and alkaloids in all three plant materials. T. cacao and P. americana, in addition, contained purine base alkaloids, triterpenoids including saponins. The aqueous extracts of the leaves showed antiplasmodial activity against the chloroquine-sensitive 3D7 P. falciparum (9.50 ± 1.38 ≤ IC50 ≤ 10.15 ± 0.45 µg/mL) and against chloroquine-resistant W2 P. falciparum strains (6.40 ± 1.94 ≤ IC50 ≤ 44.94 ± 1.12 µg/mL). The aqueous extract of T. cacao was the most active and was more active against W2 than 3D7 P. falciparum. Only T. procumbens displayed cytotoxicity (CC50<25 µg/mL). Conclusion: T. cacao, T. procumbens and P. americana possess antiplamodial activity. The activity illustrates their antimalarial potential, and provides rationale for their use in traditional malaria therapy in Ghana. It thus paves the way for further study of these plants for antiplasmodial lead compound(s)

Advances in decomposing complex metabolite mixtures using substructure- and network-based computational metabolomics approaches

Covering: up to the end of 2020 Recently introduced computational metabolome mining tools have started to positively impact the chemical and biological interpretation of untargeted metabolomics analyses. We believe that these current advances make it possible to start decomposing complex metabolite mixtures into substructure and chemical class information, thereby supporting pivotal tasks in metabolomics analysis including metabolite annotation, the comparison of metabolic profiles, and network analyses. In this review, we highlight and explain key tools and emerging strategies covering 2015 up to the end of 2020. The majority of these tools aim at processing and analyzing liquid chromatography coupled to mass spectrometry fragmentation data. We start with defining what substructures are, how they relate to molecular fingerprints, and how recognizing them helps to decompose complex mixtures. We continue with chemical classes that are based on the presence or absence of particular molecular scaffolds and/or functional groups and are thus intrinsically related to substructures. We discuss novel tools to mine substructures, annotate chemical compound classes, and create mass spectral networks from metabolomics data and demonstrate them using two case studies. We also review and speculate about the opportunities that NMR spectroscopy-based metabolome mining of complex metabolite mixtures offers to discover substructures and chemical classes. Finally, we will describe the main benefits and limitations of the current tools and strategies that rely on them, and our vision on how this exciting field can develop toward repository-scale-sized metabolomics analyses. Complementary sources of structural information from genomics analyses and well-curated taxonomic records are also discussed. Many research fields such as natural products discovery, pharmacokinetic and drug metabolism studies, and environmental metabolomics increasingly rely on untargeted metabolomics to gain biochemical and biological insights. The here described technical advances will benefit all those metabolomics disciplines by transforming spectral data into knowledge that can answer biological questions

Biodereplication of antiplasmodial extracts: application of the amazonian medicinal plant piper coruscans kunth

Improved methodological tools to hasten antimalarial drug discovery remain of interest, especially when considering natural products as a source of drug candidates. We propose a biodereplication method combining the classical dereplication approach with the early detection of potential antiplasmodial compounds in crude extracts. Heme binding is used as a surrogate of the antiplasmodial activity and is monitored by mass spectrometry in a biomimetic assay. Molecular networking and automated annotation of targeted mass through data mining were followed by mass-guided compound isolation by taking advantage of the versatility and finely tunable selectivity offered by centrifugal partition chromatography. This biodereplication workflow was applied to an ethanolic extract of the Amazonian medicinal plant Piper coruscans Kunth (Piperaceae) showing an IC50 of 1.36 ug/mL on the 3D7 Plasmodium falciparum strain. It resulted in the isolation of twelve compounds designated as potential antiplasmodial compounds by the biodereplication workflow. Two chalcones, aurentiacin (1) and cardamonin (3), with IC50 values of 2.25 and 5.5 uM, respectively, can be considered to bear the antiplasmodial activity of the extract, with the latter not relying on a heme-binding mechanism. This biodereplication method constitutes a rapid, efficient, and robust technique to identify potential antimalarial compounds in complex extracts such as plant extracts

On the structures of the penduflorines from Tabernaemontana penduliflora

The structures of the recently published monoterpene indole alkaloids penduflorines A and B (1a and 1b), isolated from Tabernaemontana penduliflora (Apocynaceae), have been revised. Rather than an inseparable mixture of two compounds, they appear to be the known alkaloid vobasine (2). Although we could not comprehensively revise the structures of penduflorines C-E due to lacking spectral data, since their structural elucidations were based on that of 1a and 1b, their structures should also be treated with caution

Exploring the chemical space of Strychnos species through a multi-informative molecular network

In the field of metabolomics, chemometrics is a domain in constant evolution. These last years, innovative techniques such as molecular networking have particularly been applied to the field of medicinal plants. As part of the ERDF project called “Tropical Plant Factory”, we apply this technique to the study of the monoterpene indole alkaloids (MIA) from plants of the genus Strychnos (Loganiaceae), largely studied in the University of Liège, but which still reserve us many surprises. Forty-four extracts of Strychnos were profiled by LC-ESI-Q-TOF MS/MS. The resulting MS/MS data were pre-processed using “MZmine 2” and were organized as a single molecular network using the GNPS online platform. The molecular network was mapped with the “Cytoscape” software. Thanks to the implementation of a specific database on the GNPS online platform (the so-called MIADB, which includes Strychnos compounds from our laboratory), the known metabolites were directly identified, allowing comparison of alkaloid composition of the investigated species and giving new insights in their composition. So, in the continuation of this work, by analyzing the molecular network, the interesting species will be highlighted, and the unknown metabolites will be targeted during the bioassay-guided fractionation. This technique could be an efficient time saving and cost-effective method for the detection of new interesting compounds in natural resources

Analyses chimioinformatiques des espèces du genre Strychnos par réseautage moléculaire : investigation de la strychnine

Depuis maintenant plus de deux siècles, les plantes du genre Strychnos, appartenant à la famille des Loganiaceae, ne cessent de susciter l’intérêt des chercheurs tant pour leurs usages traditionnels (fièvre, morsure de serpent, mal de ventre, rhumatisme, …) que pour leurs propriétés pharmacologiques, notamment leurs activités tétanisante ou curarisante, ou encore leur importante activité antiplasmodiale. Plusieurs alcaloïdes prometteurs ont déjà été étudiés et identifiés (usambarensine, dihydrousambarensine, sungucine, bisnordihydrotoxiférine, …). Pour investiguer plus loin les alcaloïdes des Strychnos, sur base de données MS/MS, un réseautage moléculaire de 44 extraits a été réalisé. Grâce à cette technique chimioinformatique, les différents métabolites ont été cartographiés selon leur ressemblance spectrale. De plus, l’implémentation de bases de données, notamment le MIADB (Monoterpene Indole Alkaloid DataBase) qui reprend une grande partie des alcaloïdes indolomonoterpéniques connus à ce jour et qui a été développée par l’Université Paris-Saclay, a permis d’identifier directement les molécules connues par comparaison des spectres MS/MS. Ainsi, 504 identifications ont été proposées, notamment la strychnine, la serpentine, la sungucine et la strychnofoline, dont certaines n’ont pas encore été décrites dans la littérature. C’est le cas de la strychnine qui a été détectée au sein de plusieurs espèces où elle n’était pas décrite comme, par exemple, les écorces de troncs de Strychnos scheffleri, de Strychnos camptoneura et de Strychnos densiflora. Pour confirmer cette identification, des analyses par chromatographie sur couche mince, par chromatographie liquide, par résonance magnétique nucléaire et par spectrométrie de masse ont été effectuées. Dans le cadre du poster, seuls les résultats des analyses des écorces de troncs du Strychnos densiflora seront présentés. Les différentes analyses orthogonales réalisées ont permis de confirmer la présence de strychnine dans les écorces de troncs du Strychnos densiflora ainsi que dans les autres espèces. Le réseautage moléculaire est donc un outil performant dans l’identification de nouveaux métabolites. En combinaison avec le fractionnement bioguidé, il sera ainsi possible d’isoler et de purifier plus efficacement les nouvelles molécules naturelles antiplasmodiales qui constitueront une source potentielle au développement de nouveaux traitements antimalariques

Investigation of the alkaloid composition of Strychnos genus using molecular networking, a mapping method for molecules

Molecular networking is a chemometric technique which is now applied to the field of medicinal plants. With the contribution of the team of Pharmacognosy from ULiege regarding compounds from plants of the Strychnos genus (Loganiaceae family), the University of Paris-Sud implemented a spectral database focused on monoterpene indole alkaloids, called MIADB, available on the GNPS online platform and on MetaboLights. This database offers the possibility to annotate extracts and to quickly discriminate unknown alkaloids by comparison of tandem mass spectra. In this way, the ERDF project « Tropical Plant Factory » has the objective of isolating new natural compounds, using this approach as an effective guidance. Therefore, the first step of my work consisted in the elaboration of a methodology to identify highly original compounds from the genus using this technique. Forty-four extracts of Strychnos, prepared with the SpeedExtractor E-914, were profiled by (UP)LC-ESI-Q-TOF-MS/MS. The resulting MS/MS data were pre-processed using the “MZmine 2” software, organized as a single molecular network through the GNPS online platform and displayed on the “Cytoscape” software. The molecular network obtained allowed to choose the interesting extracts, which alkaloids of interest will be isolated with a combination of bioassay-guided fractionation interfaced with mass-guided approach