Publications

# Publications/

OpenAccess The Essential Medicinal Chemistry of Curcumin

Journal: Journal of Medicinal Chemistry (RoMEO status: White) Published on
Categories: publications
Subjects: Pharmacognosy Phytochemistry Curcumin IMPs PAINS Review

Curcumin is a constituent (up to ∼5%) of the traditional medicine known as turmeric. Interest in the therapeutic use of turmeric and the relative ease of isolation of curcuminoids has led to their extensive investigation. Curcumin has recently been classified as both a PAINS (pan-assay interference compounds) and an IMPS (invalid metabolic panaceas) candidate. The likely false activity of curcumin in vitro and in vivo has resulted in >120 clinical trials of curcuminoids against several diseases.

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# Publications/

Hyphenating Centrifugal Partition Chromatography with Nuclear Magnetic Resonance through Automated Solid Phase Extraction

Journal: Analytical Chemistry (RoMEO status: White) Published on
Categories: publications
Subjects: Analytical Chemistry Preparative chemistry Reverse engineering Hyphenation CPC NMR SPE

Centrifugal partition chromatography (CPC) and all countercurrent separation apparatus provide chemists with efficient ways to work with complex matrixes, especially in the domain of natural products. However, despite the great advances provided by these techniques, more efficient ways of analyzing the output flow would bring further enhancement. This study describe a hyphenated approach made by coupling NMR with CPC through a hybrid-indirect coupling made possible by using a solid phase extraction (SPE) apparatus intended for high-pressure liquid chromatography (HPLC)-NMR hyphenation.

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# Publications/

Dissemination of Original NMR Data Enhances Reproducibility and Integrity in Chemical Research

Journal: Natural Product Reports (RoMEO status: Yellow) Published on
Categories: publications
Subjects: Fundamental research NMR raw data

The notion of data transparency is gaining a strong awareness among the scientific community. The availability of raw data is actually regarded as a fundamental way to advance science by promoting both integrity and reproducibility of research outcomes. Particularly, in the field of natural product and chemical research, NMR spectroscopy is a fundamental tool for structural elucidation and quantification (qNMR). As such, the accessibility of original NMR data, i.e., Free Induction Decays (FIDs), fosters transparency in chemical research and optimizes both peer review and reproducibility of reports by offering the fundamental tools to perform efficient structural verification.

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# Publications/

Integration of Molecular Networking and In-Silico MS/MS Fragmentation for Natural Products Dereplication

Journal: Analytical Chemistry (RoMEO status: White) Published on
Categories: publications
Subjects: Pharmacognosy Phytochemistry MS Fragmentation Molecular Networking Virtual pharmacognosy

Dereplication represents a key step for rapidly identifying known secondary metabolites in complex biological matrices. In this context, liquid-chromatography coupled to high resolution mass spectrometry (LC-HRMS) is increasingly used and, via untargeted data-dependent MS/MS experiments, massive amounts of detailed information on the chemical composition of crude extracts can be generated. An efficient exploitation of such data sets requires automated data treatment and access to dedicated fragmentation databases. Various novel bioinformatics approaches such as molecular networking (MN) and in-silico fragmentation tools have emerged recently and provide new perspective for early metabolite identification in natural products (NPs) research.

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# Publications/

OpenAccess Toward Structural Correctness: Aquatolide and the Importance of 1D Proton NMR FID Archiving

Journal: Journal of Organic Chemistry (RoMEO status: White) Published on
Categories: publications
Subjects: Pharmacognosy Phytochemistry NMR FID raw data Spin simulation

The revision of the structure of the sesquiterpene aquatolide from a bicyclo[2.2.0]hexane to a bicyclo[2.1.1]hexane structure using compelling NMR data, X-ray crystallography, and the recent confirmation via full synthesis exemplify that the achievement of “structural correctness” depends on the completeness of the experimental evidence. Archived FIDs and newly acquired aquatolide spectra demonstrate that archiving and rigorous interpretation of 1D 1H NMR data may enhance the reproducibility of (bio)chemical research and curb the growing trend of structural misassignments.

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# Publications/

OpenAccess Can Invalid Bioactives Undermine Natural Product-Based Drug Discovery?

High-throughput biology has contributed a wealth of data on chemicals, including natural products (NPs). Recently, attention was drawn to certain, predominantly synthetic, compounds that are responsible for disproportionate percentages of hits but are false actives. Spurious bioassay interference led to their designation as pan-assay interference compounds (PAINS). NPs lack comparable scrutiny, which this study aims to rectify. Systematic mining of 80+ years of the phytochemistry and biology literature, using the NAPRALERT database, revealed that only 39 compounds represent the NPs most reported by occurrence, activity, and distinct activity.

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# Publications/

Bioadhesive properties of enriched proanthocyanidins primers

Journal: Dental Materials (RoMEO status: Green) Published on
Categories: publications
Subjects: Pharmacognosy Phytochemistry Dentistry OPAC NMR

Plant derived proanthocyanidins are well-established compounds exhibiting high dentin biomodification potency. Among the effects, enhanced tissue biomechanics and biostability are of relevance to restorative dentistry. This study evaluated the adhesive properties of an enriched proanthocyanidin primer on the bond strength of experimental resin-based adhesives containing variable concentrations of HEMA.

# Publications/

Subtle Chemical Shifts Explain the NMR Fingerprints of Oligomeric Proanthocyanidins with High Dentin Biomodification Potency

Journal: Journal of Organic Chemistry (RoMEO status: White) Published on
Categories: publications
Subjects: Pharmacognosy Phytochemistry Dentistry OPAC NMR

The ability of certain oligomeric proanthocyanidins (OPACs) to enhance the biomechanical properties of dentin involves collagen cross-linking of the 1.3–4.5 nm wide space via protein–polyphenol interactions. A systematic interdisciplinary search for the bioactive principles of pine bark has yielded the trimeric PAC, ent-epicatechin-(4β→8)-epicatechin-(2β→O→7,4β→8)-catechin (3), representing the hitherto most potent single chemical entity capable of enhancing dentin stiffness. Building the case from two congeneric PAC dimers, a detailed structural analysis decoded the stereochemistry, spatial arrangement, and chemical properties of three dentin biomodifiers.

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# Publications/

Mimicking the Hierarchical Functions of Dentin Collagen Cross-Links with Plant Derived Phenols and Phenolic Acids

Journal: Langmuir (RoMEO status: White) Published on
Categories: publications
Subjects: Pharmacognosy Phytochemistry Dentistry Polyphenols NMR

Proanthocyanidins (PACs) are secondary plant metabolites that mediate nonenzymatic collagen cross-linking and enhance the properties of collagen based tissue, such as dentin. The extent and nature of cross-linking is influenced by the composition and specific chemical structure of the bioactive compounds present in certain PAC-rich extracts. This study investigated the effect of the molecular weight and stereochemistry of polyphenol compounds on two important properties of dentin, biomechanics, and biostability. For that, purified phenols, a phenolic acid, and some of its derivatives were selected: PAC dimers (A1, A2, B1, and B2) and a trimer (C1), gallic acid (Ga), its esters methyl-gallate (MGa) and propyl-gallate (PGa), and a pentagalloyl ester of glucose (PGG).

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# Publications/

New E-miyabenol isomer isolated from grapevine cane using centrifugal partition chromatography guided by mass spectrometry

Journal: Tetrahedron (RoMEO status: Green) Published on
Categories: publications
Subjects: Pharmacognosy Phytochemistry Vine Wine Stilbenoids Polyphenols CPC Mass Spectrometry

Stilbenoids have received increasing attention over the last two decades since the discovery of resveratrol in wine. With an ever-growing rhythm, a multitude of biological activities of naturally occurring stilbenes are being reported. In this work, we investigated minor stilbenoid compounds from Vitis vinifera stalks. The compounds were purified by means of centrifugal partition chromatography (CPC), a countercurrent-separation technique. Electrospray ionization–ion trap mass spectrometry (ESI–IT-MS) after optimization proved to be extremely efficient for the detection of these new molecules, providing both structural information for structure elucidation and a means to achieve identification even with minute amounts.

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# Publications/

Unambiguous Determination of the Absolute Configuration of Dimeric Stilbene Glucosides from the Rhizomes of Gnetum africanum

Journal: Journal of Natural Products (RoMEO status: White) Published on
Categories: publications
Subjects: Pharmacognosy Phytochemistry VCD Stereochemistry

Dimeric stilbene glucosides 1–3 [two diastereomers of (−)-gnemonoside A (1a and 1b), (−)-gnemonoside C (2), and (−)-gnemonoside D (3)] as well as a mixture of the two enantiomers of gnetin C (4) were isolated from the rhizomes of Gnetum africanum. The two enantiomers of gnetin C, (+)-4 and (−)-4, were obtained from the aglycones of 1a and 1b, respectively. The configurations of these stilbenoids were investigated by NMR and vibrational circular dichroism (VCD) experiments.

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# Publications/

OpenAccess Essential Parameters for Structural Analysis and Dereplication by 1H NMR Spectroscopy

Journal: Journal of Natural Products (RoMEO status: White) Published on
Categories: publications
Subjects: Pharmacognosy Phytochemistry NMR Spin simulation

The present study demonstrates the importance of adequate precision when reporting the δ and J parameters of frequency domain 1H NMR (HNMR) data. Using a variety of structural classes (terpenoids, phenolics, alkaloids) from different taxa (plants, cyanobacteria), this study develops rationales that explain the importance of enhanced precision in NMR spectroscopic analysis and rationalizes the need for reporting Δδ and ΔJ values at the 0.1–1 ppb and 10 mHz level, respectively.

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# Publications/

Comparative Analyses of Stilbenoids in Canes of Major Vitis vinifera L. Cultivars

Grapevine canes are rich in resveratrol and its complex derivatives. These compounds have many biological activities and are needed mainly for health purposes. Canes, which are often wasted, can be used to produce these high-value compounds at low cost. We studied sixteen Vitis vinifera L. cultivars among the most widely cultivated ones worldwide. Polyphenols were extracted from their canes and identified by liquid chromatography–nuclear magnetic resonance spectroscopy. We accurately determined the content of E-ε-viniferin, E-resveratrol, E-piceatannol, and vitisin B and, for the first time, that of hopeaphenol and miyabenol C.

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# Publications/

Inhibitory Activity of Plant Stilbenoids against Nitric Oxide Production by Lipopolysaccharide-Activated Microglia

Journal: Planta Medica (RoMEO status: Blue) Published on
Categories: publications
Subjects: Pharmacognosy Phytochemistry Vine Wine Stilbenoids Polyphenols Bioactivity

Microglia-driven inflammatory processes are thought to play an important role in ageing and several neurological disorders. Since consumption of a diet rich in polyphenols has been associated with anti-inflammatory and neuroprotective effects, we studied the effects of twenty-five stilbenoids isolated from Milicia excelsa, Morus alba, Gnetum africanum, and Vitis vinifera. These compounds were tested at 5 and 10 µM on BV-2 microglial cells stimulated with bacterial lipopolysaccharide. Ten stilbenoids reduced lipopolysaccharide-induced nitric oxide production at 5 and/or 10 µM.

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# Publications/

Centrifugal partition chromatography applied to the isolation of oak wood aroma precursors

Journal: Food Chemistry (RoMEO status: Green) Published on
Categories: publications
Subjects: CPC Oak Wood Flavor Wine

Flavours extracted from oak wood during barrel ageing contribute to the organoleptic character of wines and spirits. The aim of this work was to identify the glycosidic precursors of the key volatile compounds responsible for oak wood aroma. Oak extract is a very complex matrix and, furthermore, precursors are present in very small quantities. Preparative centrifugal partition chromatography (CPC) is a promising solution for purifying the oak extract. The solvent system was selected on the basis of the partition coefficient of glycosidase enzyme activity (Kca).

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# Publications/

Chemical dereplication of wine stilbenoids using high performance liquid chromatography–nuclear magnetic resonance spectroscopy

Journal: Journal of Chromatography A (RoMEO status: Green) Published on
Categories: publications
Subjects: Analytical Chemistry Dereplication LC-NMR Vine Wine

Wine is a major dietary source of numerous potentially health promoting stilbenoids that have been the subject of many qualitative and quantitative studies. However, our initial HPLC–MS analyses of crude wine samples demonstrated the presence of compounds with molecular weights matching characteristic stilbenoid dimers, trimers, and tetramers that were unaccounted for in the literature. Due to the likelihood that these are known compounds, a chemical dereplication method is highly desirable. We developed such a method using LC-DAD–MS monitored fractionation steps, using adsorption and centrifugal partition chromatography (CPC), to obtain fractions rich in stilbenoids for analysis in stopped-flow LC–NMR.

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# Publications/

Stilbenoid Profiles of Canes from Vitis and Muscadinia Species

We present stilbenoid profiles of canes from 16 grapevines. Fifteen stilbenoids were obtained through isolation and structure identification using MS, NMR, and [α]D or as commercial standards. An HPLC–UV method for the simultaneous quantification of nine of these stilbenoids was developed and applied to canes of Vitis amurensis, Vitis arizonica, Vitis berlandieri, Vitis betulifolia, Vitis cinerea, Vitis × champini, Vitis × doaniana, Vitis labrusca, Vitis candicans (syn. Vitis mustangensis), Vitis riparia, Vitis rupestris, Vitis vinifera, Muscadinia rotundifolia, and a V.

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# Publications/

Phenolics and their antifungal role in grapevine wood decay: Focus on the Botryosphaeriaceae family

The interaction between Vitis vinifera and trunk disease fungi requires better understanding. We studied the role of phenolics as possible plant defense compounds in this context. The impact of 24 grapevine phenolic compounds was determined on 6 major wood decay fungi by an in vitro agar plate assay. Hydroxystilbenoids, especially oligomers such as miyabenol C, isohopeaphenol, and vitisin A and B, greatly reduced the growth of the fungi, except that of Phaeoacremonium aleophilum.

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# Publications/

Development of hybrid elution systems for efficient purification of stilbenoids using centrifugal partition chromatography coupled to mass spectrometry

Journal: Journal of Chromatography A (RoMEO status: Green) Published on
Categories: publications
Subjects: Analytical Chemistry Preparative chemistry Hyphenation CPC MS back-step Vine Wine

The phytochemical study of the root extract of the stilbenoid-rich Vitis riparia × Vitis berlandieri grapevine was carried out by centrifugal partition chromatography (CPC). For this reason, we developed a new elution mode we named back-step, which allowed us to obtain cleaner fractions and a more efficient separation process when used in conjunction with a classical elution approach. Three hydroxystilbenes: (E)-resveratrol, (E)-ɛ-viniferin and (E)-vitisin C, with greater than 90% purity were thus obtained through such process, with minimal sample handling and purification steps.

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