Whether chemists or biologists, researchers dealing with metabolomics require tools to decipher complex mixtures. As a part of metabolomics and initially dedicated to identifying bioactive natural ...products, dereplication aims at reducing the usual time-consuming process of known compounds isolation. Mass spectrometry and nuclear magnetic resonance are the most commonly reported analytical tools during dereplication analysis. Though it has low sensitivity, 13C NMR has many advantages for such a study. Notably, it is nonspecific allowing simultaneous high-resolution analysis of any organic compounds including stereoisomers. Since NMR spectrometers nowadays provide useful data sets in a reasonable time frame, we have embarked upon writing software dedicated to 13C NMR dereplication. The present study describes the development of a freely distributed algorithm, namely MixONat and its ability to help researchers decipher complex mixtures. Based on Python 3.5, MixONat analyses a {1H}-13C NMR spectrum optionally combined with DEPT-135 and 90 datato distinguish carbon types (i.e., CH3, CH2, CH, and C)as well as a MW filtering. The software requires predicted or experimental carbon chemical shifts (δc) databases and displays results that can be refined based on user interactions. As a proof of concept, this 13C NMR dereplication strategy was evaluated on mixtures of increasing complexity and exhibiting pharmaceutical (poppy alkaloids), nutritional (rosemary extracts) or cosmetics (mangosteen peel extract) applications. Associated results were compared with other methods commonly used for dereplication. MixONat gave coherent results that rapidly oriented the user toward the correct structural types of secondary metabolites, allowing the user to distinguish between structurally close natural products, including stereoisomers.
Accumulation in tissues and serum of advanced glycation end-products (AGEs) plays an important role in pathologies such as Alzheimer’s disease or, in the event of complications of diabetes, ...atherosclerosis or renal failure. Therefore, there is a potential therapeutic interest in compounds able to lower intra and extracellular levels of AGEs. Among them, natural antioxidants (AO) with true anti-AGEs capabilities would represent good candidates for development. The purpose of this study was to evaluate the AO and anti-AGEs potential of a propolis batch and then to identify the main compounds responsible for these effects. In vivo, protein glycation and oxidative stress are closely related. Thus, AO and antiglycation activities were evaluated using both DPPH and ORAC assays, respectively, as well as a newly developed automated anti-AGEs test. Several propolis extracts exhibited very good AO and anti-AGEs activities, and a bioguided fractionation allowed us to identify pinobanksin-3-acetate as the most active component.
Chemical investigation of the emblematic Catharanthus roseus led to the discovery of trirosaline (1), the first example of a tris-ajmalicine-type monoterpene indole alkaloid and the first natural ...trimeric MIA ever reported from this deeply dug plant species. Its structure was primarily elucidated based on NMR and HRESIMS analyses, and the nature of its unique intermonomeric linkages was firmly confirmed based on a combination of empirical computation and ML-J-DP4 study. Its absolute configuration was mitigated by comparison of experimental and TDDFT-simulated electronic circular dichroism (ECD) spectra. A possible biosynthetic pathway for trirosaline (1) was postulated.
Phytochemical investigation on the fruits of Mesua lepidota (Calophyllaceae) led to the isolation of seven new phenylcoumarin derivatives named lepidotols A–E (1–5) and lepidotins A and B (6, 7). ...These structures were elucidated by spectroscopic and spectrometric methods including UV, NMR, and HRMS. Lepidotol A (1), the major compound, was evaluated for its inhibitory effect on inflammation and immunity using endothelial cell-based cellular assays. At 10 μM, 1 exhibited an anti-inflammatory activity, with a significant inhibition of vascular cell adhesion molecule 1 and intercellular adhesion molecule 1 expression induced by tumor necrosis factor-α. Lepidotol A also showed a mild immunosuppressive effect, with inhibition of the major histocompatibility complex molecules, namely, human leukocyte antigen (HLA)-DR and HLA-E.
Phytochemical investigation of the root extracts of Hypericum perforatum led to the isolation of two biphenyl derivatives named hyperbiphenyls A and B (1 and 2) and four known xanthones (3–6). These ...structures were elucidated by spectroscopic and spectrometric methods including UV, NMR, and HRMS. The absolute configuration of the biphenyl derivatives was defined by two different approaches: biomimetic total synthesis of racemic hyperbiphenyl A followed by 1H and 19F NMR Mosher’s esters analysis and stereoselective total synthesis of hyperbiphenyl B, permitting assignment of the S absolute configuration for both compounds. The bioactivity of compounds 1–6 toward a set of biomolecules, including major histocompatibility complex (MHC) molecules expressed on vascular endothelial cells, was measured. The results showed that the major xanthone, i.e., 5-O-methyl-2-deprenylrheediaxanthone B (3), is a potent inhibitor of MHC that efficiently reduces HLA-E, MHC-II, and MICA biomolecules on cell surfaces.
Introduction
Xanthones are metabolites with a variety of biological properties. The Clusiaceae family, which until recently included the genus Calophyllum, is recognised for its production of ...monohydroxylated and polyhydroxylated xanthones. Presently, C. brasiliense is the only Calophyllum spp. known to occur in the Yucatan peninsula.
Objective
To use a combination of traditional phytochemical methods and carbon‐13 nuclear magnetic resonance (13C‐NMR) dereplication analysis to identify xanthones in the stem bark of C. brasiliense.
Material and methods
Initial fractionation and purification of the stem bark extract of C. brasiliense produced macluraxanthone (1). Additional xanthones, together with chromanones and terpenoids, were identified using 13C‐NMR dereplication analysis in different semipurified fractions obtained from the low and medium polarity fractions of the stem bark extract of C. brasiliense.
Results
Initial identification of macluraxanthone (1) was confirmed by 13C‐NMR dereplication analysis; additionally, 13C‐NMR dereplication analysis allowed the identification of a number of monohydroxylated and polyhydroxylated xanthones, together with chromanones and terpenoids.
Conclusion
This study confirms C. brasiliense as a rich source of xanthones and the 13C‐NMR dereplication analysis as a suitable method to quickly identify the presence of different families of secondary metabolites in semipurified fractions.
Calophyllum brasiliense is recognised for its production of xanthones having different biological activities. In this investigation, a combination of phytochemical methods and carbon‐13 nuclear magnetic resonance (13C‐NMR) dereplication analysis allowed the identification of a number of monohydroxylated and polyhydroxylated xanthones, together with chromanones and terpenoids, from the stem bark extract of the plant.
Isolation and identification of amentoflavone 1 and 3-methoxy-2-hydroxyxanthone 2 as very potent advanced glycation end-products (AGEs) inhibitors and of 3,4-dihydroxy-tetrahydrofuran-3-carboxylic ...acid 3 and flavoramulone 8 as a new product from Calophyllum flavo-ramulum MeOH leaf extract. Display omitted
► Extracts from Clusiaceae/Calophyllaceae were tested for their antiAGEs potential. ► Calophyllum flavoramulum MeOH leaf extract was selected. ► Its bioguided fractionation led to identify 1 and 2 as very potent AGEs inhibitors. ► Two new products 3 and 8 were also isolated and described.
Advanced glycation end-products (AGEs) are associated with many pathogenic disorders such as Alzheimer’s disease, pathogenesis of diabetes, atherosclerosis or endothelial dysfunction leading to cardiovascular events. Clusiaceae and Calophyllaceae families are rich in compounds like polyphenols which are able to inhibit their formation and are therefore of great interest. Calophyllum flavoramulum Hend. & Wyatt-Sm., a native Malaysian plant, was selected after an anti-AGEs screening conducted on DCM and MeOH extracts from plants belonging to these aforementioned families. In a first study, bioguided fractionation of the MeOH leaf extract of C. flavoramulum afforded amentoflavone, 3-methoxy-2-hydroxyxanthone, 3,4-dihydroxy-tetrahydrofuran-3-carboxylic acid, quercitrin, 3,4-dihydroxybenzoic acid, canophyllol and apetalactone. Amentoflavone and 3-methoxy-2-hydroxyxanthone were found to be very potent (IC50=0.05 and 0.06mM respectively), while anti-AGEs activities of quercitrin and 3,4-dihydroxybenzoic acid appeared as moderately strong (IC50=0.5mM). In a second study, a systematic phytochemical study of the cyclohexane, DCM and EtOAc extracts obtained from the same plant was conducted to isolate the following products: flavoramulone, 6-deoxyjacareubin, rheediachromenoxanthone, 2,3-dihydroamentoflavone and benzoic acid. 3,4-Dihydroxy-tetrahydrofuran-3-carboxylic acid and flavoramulone were isolated for the first time and their structures were identified by means of IR, MS and NMR spectrometries.
Modulation of major histocompatibility complex (MHC) expression using drugs has been proposed to control immunity. Phytochemical investigations on
species have allowed the isolation of bioactive ...compounds such as polycyclic polyprenylated acylphloroglucinols (PPAPs). PPAPs such as guttiferone J (
), display anti-inflammatory and immunoregulatory activities while garcinol (
) is a histone acetyltransferases (HAT) p300 inhibitor. This study reports on the isolation, identification and biological characterization of two other PPAPs, i.e., xanthochymol (
) and guttiferone F (
) from
, sharing structural analogy with guttiferone J (
) and garcinol (
). We show that PPAPs
-
efficiently downregulated the expression of several MHC molecules (HLA-class I, -class II, MICA/B and HLA-E) at the surface of human primary endothelial cells upon inflammation. Mechanistically, PPAPs
-
reduce MHC proteins by decreasing the expression and phosphorylation of the transcription factor STAT1 involved in MHC upregulation mediated by IFN-γ. Loss of STAT1 activity results from inhibition of HAT CBP/p300 activity reflected by a hypoacetylation state. The binding interactions to p300 were confirmed through molecular docking. Loss of STAT1 impairs the expression of CIITA and GATA2 but also TAP1 and Tapasin required for peptide loading and transport of MHC. Overall, we identified new PPAPs issued from
with potential immunoregulatory properties.
Self-assembled monolayers (SAMs) that contain fluorophore units are nowadays widely used to tune surface properties and design new chemical sensor chips. It is well-known that the nature of the ...substrate may strongly interfere with the emission properties of the grafted molecules, but the organization of the monolayer may also have an important role. To study the influence of the SAM organization on the luminescence properties, we prepared different coumarin-based derivatives endowed with tethered chains of different lengths and elaborated the corresponding SAMs on glass slides. Besides SAM structural characterizations by atomic force microscopy and X-ray reflectivity, we carried out contact angle measurements and applied the Van Oss–Chaudhury–Good theory, which was rarely used previously for self-assembled monolayers. As expected, by increasing the tethered chain length, a higher surface coverage, a higher degree of organization, and a stronger molecular packing were observed. However, it appears to facilitate the self-quenching process, and thus, this strongly affects the fluorescent properties of the SAMs.
En association à des règles hygiéno-diététiques, quelques plantes médicinales mais aussi certains médicaments et compléments alimentaires à base de plantes peuvent soulager les troubles urogénitaux ...importunant fréquemment les femmes, avec un rapport bénéfice-risque favorable. Une sélection de solutions peut être proposée pour soulager les infections urinaires récidivantes, le syndrome prémenstruel ou les bouffées de chaleur sur la base des données scientifiques et cliniques disponibles. Les précautions d’emploi doivent systématiquement être rappelées.
Combined with dietary and lifestyle measures, some medicinal plants as well as certain medications and plant-based food supplements can relieve genitourinary disorders frequently inconveniencing women, with a favourable risk-benefit ratio. A selection of solutions can be offered to fight against recurring urinary infections, premenstrual syndrome or hot flushes, on the basis of available scientific and clinical data. The pharmacist must systematically remind patients of the precautions to take.
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