The three pillars of natural product dereplication. Alkaloids from the bulbs of Urceolina peruviana (C. Presl) J.F. Macbr. as a preliminary test case

open access articleThe role and importance of the identification of natural products are first discussed in the perspective of the study of secondary metabolites. The rapid identification of already reported compounds, or structural dereplication, is recognized as a key element in natural product chemistry. The biological taxonomy of metabolite producing organisms, the knowledge of metabolite molecular structures, and the availability of metabolite spectroscopic signatures are considered as the three pillars of structural dereplication. The role and the construction of databases is illustrated by references to the KNApSAcK, UNPD, CSEARCH, and COCONUT databases, and by the importance of calculated taxonomic and spectroscopic data as substitutes for missing or lost original ones. Two NMR-based tools, the PNMRP database that derives from UNPD, and KnapsackSearch, a database generator that provides taxonomically focused libraries of compounds, are proposed to the community of natural product chemists. The study of the alkaloids from Urceolina peruviana, a plant from the Andes used in traditional medicine for antibacterial and anticancer actions, has given the opportunity to test different approaches to dereplication, favoring the use of publicly available data sources

Evaluation of Schistosoma mansoni cercaricidal activity of Solamargine a steroid glycoalkaloid from Solanum syzybrilifolium

ABSTRACT- The cercaricidal activity of a mixed solamargine (1) and β-solamarine (2) solution were directly tested against Schistosoma mansoni cercariae and a time-concentration relationship was observed; the concentrations needed to kill all cercariae (LC100) within 10 min of exposure were 0.01 mg/mL. Mixed solamargine (1) and β-solamarine (2) solution have a high level of cercaricidal activity against free swimming cercariae and it seems to be ecologically safe, since it is known to have very low toxicity to fish. The possible use of such sublethal concentrations in schistosomiasis transmission sites as an oriented promising technique to control this parasite and to minimize or prevent water pollution with pesticides

Saponins and flavonoid glycosides from the leaves of Ziziphus mauritiana Lam. native of a forest area of Ivory Coast

International audienceZiziphus mauritiana Lam (Rhamnaceae) is traditionally used in the treatment of various ailments. The aim of the present study is to identify the major compounds of the methanol extract of the leaves of Ziziphus mauritiana growing in Ivory Coast. The methanol extract of this plant was purified by combining silica gel and RP18 HPLC to give an undescribed compounds, 6’’’-O-malonyl-ziziphus saponin I (1) along with nine known compounds from which two saponins, six flavonoids, and one chalcone derivate.The structures of these compounds were elucidated by analysis of 1D- and 2D-NMR spectroscopic data and mass spectrometry (HR-ESI-MS). A part from zizyphus saponin I (2), all the others compounds were isolated for the first time from the leaves of this species

Triterpene saponins from Silene gallica collected in North-Eastern Algeria

International audienceEleven previously undescribed triterpene saponins, named silenegallisaponin A-K (1–11), were isolated from the aerial parts of Silene gallica L. Their structures were elucidated by analysis of 1D and 2D-NMR spectroscopic data and mass spectrometry (HR-ESI-MS). The saponins comprised caulophyllogenin, echinocystic acid, or quillaic acid substituted at C-3 by a β-d-glucuronic acid or β-d-galactopyranosyl-(1 → 3)-β-d-glucuronopyranoside and at C-28 by a β-d-fucopyranose substituted at C-2 by a β-d-glucose and at C-3 by a β-d-glucose or a β-d-quinovose

Purification of a modified cyclosporine A by co-current centrifugal partition chromatography: Process development and intensification

International audienceSynthetic hydrophobic non-ionizable peptides are not soluble in most common solvents and are thus difficult to purify by preparative reversed-phase HPLC, normally used for industrial production. The challenge exists to develop alternative purification chromatographic processes using suitable solvents and providing good yields, high purity and sufficient productivity. A 11mer hydrophobic synthetic modified cyclosporine, showing an anti-HIV activity, was successfully purified by centrifugal partition chromatography using the biphasic solvent system heptane/ethyl acetate/acetone/methanol/water (1:2:2:1:2, v/v). A 5% co-current elution - made possible by the liquid nature of the two phases - has been used in order to avoid hydrodynamic instabilities mainly due to the physico-chemical properties of the target peptide. This original solution was developed after the study of the effect of the peptide on the hydrodynamic behavior of the two phases during the separation, and the visualization of the flow patterns using the Visual-CPC device. Critical impurities were efficiently eliminated and the peptide was recovered in high yield and high productivity achieving the specifications requirements (C) 2013 Elsevier B.V. All rights reserved

Improving the chemical profiling of complex natural extracts by joint 13C NMR and LC-HRMS2 analysis and the querying of in silico generated chemical databases

The chemical profiling of complex natural mixtures emerges as a pivotal avenue of investigation for the discovery of new bioactive compounds. It requires a dereplication step generally based either on liquid chromatography-high resolution tandem mass spectrometry (LC-HRMS2) or on nuclear magnetic resonance (NMR) to quickly identify known compounds. The high sensitivity of MS results in numerous but sometimes incorrect candidate compounds, whereas the greater universality of NMR leads to fewer but more accurate annotations. These two analytical techniques are rarely used in combination despite their complementarity. This study focuses on the chemical profiling of Larix decidua (Pinaceae) bark by joint LC-HRMS2 and 13C NMR data analysis and by querying custom in silico-generated chemical databases. MS-based dereplication allowed the annotation of 135 MS2 spectra with at least two different annotation tools. Twenty-five compounds were annotated in parallel by NMR spectra analysis, including two previously undescribed myrtenic acid derivatives. Sixteen of these compounds were already reported in the Pinaceae family. Twelve compounds were jointly annotated with a high confidence level by comparing LC-HRMS2 and 13C NMR dereplication results, including compounds not reported to date in Larix decidua. Our results show the benefits brought by combining LC-HRMS2 and 13C NMR data and by querying custom in silico chemical databases to enhance the confidence level of data annotation during the chemical profiling of complex natural extracts

Investigation of antiparasitic activity of ten European tree bark extracts on Toxoplasma gondii and bioguided identification of triterpenes in Alnus glutinosa barks

International audienceToxoplasmosis is a worldwide parasitosis that affects one-third of the population. People at risk, such as immunocompromised patients (AIDS, chemotherapy treatment) or fetuses (maternal-fetal transmission) can develop severe forms of the disease. The antiparasitic activity of extracts of different polarities ( n -heptane, MeOH, MeOH/H 2 O) of ten tree species endemics to temperate regions was investigated against Toxoplasma gondii infection in vitro . Our results showed that the n -heptane extract of the black alder ( Alnus glutinosa ) exhibited a significant antiparasitic activity without any cytotoxicity at the tested concentrations, with an IC 50 of up to 25.08 μg/mL and a selectivity index higher than 3.99. The chemical profiling of this extract revealed triterpenes as major constituents. The ability of commercially available triterpene (betulin, betulinic acid, and betulone) to inhibit the growth of T. gondii was evaluated and showed growth inhibition rates of 44%, 49%, and 99% at 10 μM, respectively

Potentiel anti-Toxoplasma gondii de triterpènes de type lupane de l’écorce de l’aulne glutineux, Alnus glutinosa, et identification d’une cible potentielle par docking inverse.

International audienceToxoplasmosis is a worldwide parasitosis that is generally benign. The infestation may pose a risk to immunocompromized patients and to fetuses when pregnant women have recently seroconverted. Current treatments have numerous side effects and chemoresistance is emerging, hence the need to find new anti-Toxoplasma gondii substances. This study focuses on the antiparasitic potential of lupane-type pentacyclic triterpenes isolated from the bark of black alder (Alnus glutinosa), as well as the hypothesis of their macromolecular target by an original method of reverse docking. Among the isolated triterpenes, betulone was the most active compound with an IC50 of 2.7 ± 1.2 μM, a CC50 greater than 80 μM, and a selectivity index of over 29.6. An additional study of the anti-T. gondii potential of commercially available compounds (betulonic acid methyl ester and betulonic acid) showed the important role of the C3 ketone function and the C28 oxidation level on the lupane-type triterpene in the antiparasitic activity since their IC50 and CC50 were similar to that of betulone. Finally, the most active compounds were subjected to the AMIDE reverse docking workflow. A dataset of 87 T. gondii proteins from the Protein Data Bank was created. It identified calcium-dependent protein kinase CDPK3 as the most likely target of betulin derivatives.La toxoplasmose est une parasitose mondiale, généralement bénigne. Les personnes à risque sont les patients immunodéprimés et les fœtus chez les femmes enceintes nouvellement séroconverties. Les traitements actuels ont de nombreux effets secondaires et des phénomènes de chimiorésistance apparaissent, d’où la nécessité de trouver de nouvelles substances actives contre T. gondii . Cette étude porte sur le potentiel antiparasitaire des triterpènes pentacycliques de type lupane isolés de l’écorce de l’aulne glutineux ( Alnus glutinosa ) et formule une hypothèse quant à leur cible protéique par l’utilisation d’une méthode originale de docking inverse. Parmi les triterpènes isolés, la bétulone s’est révélée être la plus active avec une CI 50 de 2,7 μM ± 1,2 μM, une CC 50 supérieure à 80 μM et un indice de sélectivité supérieur à 29,6. L’étude complémentaire du potentiel anti- T. gondii de composés disponibles commercialement et analogues à la bétulone (acide bétulonique et methyl ester de l’acide bétulonique) a montré le rôle important de la fonction cétone en C3 et du degré d’oxydation de la position 28 du squelette triterpénique de type lupane dans l’activité antiparasitaire puisque leurs CI 50 et CC 50 étaient similaires aux valeurs rencontrées pour la bétulone. Enfin, les composés les plus actifs ont été soumis au flux de travail de docking inverse d’AMIDE. Un ensemble de 87 protéines de T. gondii de la Protein Data Bank a été créé. La protéine kinase calcium dépendante CDPK3 a été identifiée comme la cible la plus probable des dérivés de la bétuline