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)

Recherche de composés à activité antiplasmodiale à partir de la biodiversité malgache

Dans le cadre de la recherche de nouveaux composés à activité antiplasmodiale, deux plantes de Madagascar ont été étudiées : Pyrostria major (Rubiaceae) et Gonioma malagasy (Apocynaceae). Leurs extraits acétate d éthyle et alcaloïdique ont montré une activité antiplasmodiale significative vis-à-vis de la souche chloroquino-résistante FcB1 lors d un criblage préliminaire. L étude phytochimique des feuilles de P. major a conduit à l isolement du b sitostérol ainsi que de huit nouveaux diarylheptanoïdes glycosylés, décrits pour la première fois dans une plante appartenant à la famille des Rubiaceae. L activité antiplasmodiale de l extrait AcOEt des feuilles est probablement due à la présence du b sitostérol. Cette activité serait due à l effet stomatocytogénique provoqué par cette famille de composés. L utilisation de l "Exciton chirality" a permis de déterminer la configuration absolue des diarylheptanoïdes glycosylés isolés. Cette étude structurale nous a permis d obtenir d une part, deux composés antiplasmodiaux sélectifs et non cytotoxiques et d autre part, un composé antileishmanien et un autre antitrypanosomal. L étude de l extrait alcaloïdique de G. malagasy a conduit à l isolement d une nouvelle série chimique, "les goniomedines". Ces dernières sont caractérisées par un squelette bisindolique constitué de deux monomères dihydroindoliques reliés par une unité dihydropyrane. Une étude configurationnelle basée sur le calcul théorique de spectres de dichroïsme circulaire ainsi que sur des considérations biogénétiques, a permis la détermination de leur configuration absolue. Parmi ces composés, un seul a montré une activité antiplasmodiale significative.As part of the search for new compounds with antiplasmodial activity, two malagasy plants were studied: Pyrostria major (Rubiaceae) and Gonioma malagasy (Apocynaceae). The Ethyl acetate and alkaloidic extracts showed significant antiplasmodial activity against the chloroquine-resistant strain FcB1 during a preliminary screening. The phytochemical study of the leaves of P. major has led to the isolation of b-sitosterol together with eight new diarylheptanoid glucoside, described for the first time in a plant belonging to the Rubiaceae family. The antiplasmodial activity of the EtOAc extract of the leaves is probably due to the presence of b-sitosterol. This activity is due to the stomatocytogenic effect caused by this family of compound. The use of the "exciton chirality" has determined the absolute configuration of the natural diarylheptanoid glucoside. This structural study allowed us to obtain, two selective antiplasmodial and non-cytotoxic compounds, as well as potential antileishmanial and antitrypanosomal compounds. The study of the alkaloidic extract of G. malagasy led to the isolation of a novel chemical series, "The goniomedines." They are characterized by a bisindole backbone consisting of two monomers connected by a dihydropyran unit. Their absolute configurations were deduced following the comparison of experimental and theoretically calculated ECD spectra and through biogenetic considerations. Among these compounds, only one showed a significant antiplasmodial activity.PARIS11-SCD-Bib. électronique (914719901) / SudocSudocFranceF

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

Recherche de composés à activité antiplasmodiale à partir de la biodiversité malgache

As part of the search for new compounds with antiplasmodial activity, two malagasy plants were studied: Pyrostria major (Rubiaceae) and Gonioma malagasy (Apocynaceae). The Ethyl acetate and alkaloidic extracts showed significant antiplasmodial activity against the chloroquine-resistant strain FcB1 during a preliminary screening. The phytochemical study of the leaves of P. major has led to the isolation of β-sitosterol together with eight new diarylheptanoid glucoside, described for the first time in a plant belonging to the Rubiaceae family. The antiplasmodial activity of the EtOAc extract of the leaves is probably due to the presence of β-sitosterol. This activity is due to the stomatocytogenic effect caused by this family of compound. The use of the "exciton chirality" has determined the absolute configuration of the natural diarylheptanoid glucoside. This structural study allowed us to obtain, two selective antiplasmodial and non-cytotoxic compounds, as well as potential antileishmanial and antitrypanosomal compounds. The study of the alkaloidic extract of G. malagasy led to the isolation of a novel chemical series, "The goniomedines." They are characterized by a bisindole backbone consisting of two monomers connected by a dihydropyran unit. Their absolute configurations were deduced following the comparison of experimental and theoretically calculated ECD spectra and through biogenetic considerations. Among these compounds, only one showed a significant antiplasmodial activity.Dans le cadre de la recherche de nouveaux composés à activité antiplasmodiale, deux plantes de Madagascar ont été étudiées : Pyrostria major (Rubiaceae) et Gonioma malagasy (Apocynaceae). Leurs extraits acétate d’éthyle et alcaloïdique ont montré une activité antiplasmodiale significative vis-à-vis de la souche chloroquino-résistante FcB1 lors d’un criblage préliminaire. L’étude phytochimique des feuilles de P. major a conduit à l’isolement du β sitostérol ainsi que de huit nouveaux diarylheptanoïdes glycosylés, décrits pour la première fois dans une plante appartenant à la famille des Rubiaceae. L’activité antiplasmodiale de l’extrait AcOEt des feuilles est probablement due à la présence du β sitostérol. Cette activité serait due à l’effet stomatocytogénique provoqué par cette famille de composés. L’utilisation de l’"Exciton chirality" a permis de déterminer la configuration absolue des diarylheptanoïdes glycosylés isolés. Cette étude structurale nous a permis d’obtenir d’une part, deux composés antiplasmodiaux sélectifs et non cytotoxiques et d’autre part, un composé antileishmanien et un autre antitrypanosomal. L’étude de l’extrait alcaloïdique de G. malagasy a conduit à l’isolement d’une nouvelle série chimique, "les goniomedines". Ces dernières sont caractérisées par un squelette bisindolique constitué de deux monomères dihydroindoliques reliés par une unité dihydropyrane. Une étude configurationnelle basée sur le calcul théorique de spectres de dichroïsme circulaire ainsi que sur des considérations biogénétiques, a permis la détermination de leur configuration absolue. Parmi ces composés, un seul a montré une activité antiplasmodiale significative

Search for antiplasmodial compounds from the malagasy biodiversity

Dans le cadre de la recherche de nouveaux composés à activité antiplasmodiale, deux plantes de Madagascar ont été étudiées : Pyrostria major (Rubiaceae) et Gonioma malagasy (Apocynaceae). Leurs extraits acétate d’éthyle et alcaloïdique ont montré une activité antiplasmodiale significative vis-à-vis de la souche chloroquino-résistante FcB1 lors d’un criblage préliminaire. L’étude phytochimique des feuilles de P. major a conduit à l’isolement du β sitostérol ainsi que de huit nouveaux diarylheptanoïdes glycosylés, décrits pour la première fois dans une plante appartenant à la famille des Rubiaceae. L’activité antiplasmodiale de l’extrait AcOEt des feuilles est probablement due à la présence du β sitostérol. Cette activité serait due à l’effet stomatocytogénique provoqué par cette famille de composés. L’utilisation de l’"Exciton chirality" a permis de déterminer la configuration absolue des diarylheptanoïdes glycosylés isolés. Cette étude structurale nous a permis d’obtenir d’une part, deux composés antiplasmodiaux sélectifs et non cytotoxiques et d’autre part, un composé antileishmanien et un autre antitrypanosomal. L’étude de l’extrait alcaloïdique de G. malagasy a conduit à l’isolement d’une nouvelle série chimique, "les goniomedines". Ces dernières sont caractérisées par un squelette bisindolique constitué de deux monomères dihydroindoliques reliés par une unité dihydropyrane. Une étude configurationnelle basée sur le calcul théorique de spectres de dichroïsme circulaire ainsi que sur des considérations biogénétiques, a permis la détermination de leur configuration absolue. Parmi ces composés, un seul a montré une activité antiplasmodiale significative.As part of the search for new compounds with antiplasmodial activity, two malagasy plants were studied: Pyrostria major (Rubiaceae) and Gonioma malagasy (Apocynaceae). The Ethyl acetate and alkaloidic extracts showed significant antiplasmodial activity against the chloroquine-resistant strain FcB1 during a preliminary screening. The phytochemical study of the leaves of P. major has led to the isolation of β-sitosterol together with eight new diarylheptanoid glucoside, described for the first time in a plant belonging to the Rubiaceae family. The antiplasmodial activity of the EtOAc extract of the leaves is probably due to the presence of β-sitosterol. This activity is due to the stomatocytogenic effect caused by this family of compound. The use of the "exciton chirality" has determined the absolute configuration of the natural diarylheptanoid glucoside. This structural study allowed us to obtain, two selective antiplasmodial and non-cytotoxic compounds, as well as potential antileishmanial and antitrypanosomal compounds. The study of the alkaloidic extract of G. malagasy led to the isolation of a novel chemical series, "The goniomedines." They are characterized by a bisindole backbone consisting of two monomers connected by a dihydropyran unit. Their absolute configurations were deduced following the comparison of experimental and theoretically calculated ECD spectra and through biogenetic considerations. Among these compounds, only one showed a significant antiplasmodial activity

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