Publications by authors named "Emerson F Queiroz"

29 Publications

  • Page 1 of 1

Kaempferol-3-O-α-(3,4-di-E-p-coumaroyl)-rhamnopyranoside from Nectandra oppositifolia releases Ca from intracellular pools of Trypanosoma cruzi affecting the bioenergetics system.

Chem Biol Interact 2021 Sep 16;349:109661. Epub 2021 Sep 16.

Center of Natural Sciences and Humanities, Federal University of ABC, Santo Andre, SP, 09210-180, Brazil. Electronic address:

Phytochemical analysis of EtOH extract from leaves of Nectandra oppositifolia afforded three flavonoids: kaempferol (1), kaempferol-3-O-α-rhamnopyranoside (2) and kaempferol-3-O-α-(3,4-di-E-p-coumaroyl)-rhamnopyranoside (3), which were characterized by NMR and ESI-HRMS. When tested against the protozoan parasite Trypanosoma cruzi, the etiologic agent of Chagas disease, flavonoids 1 and 3 were effective to kill the trypomastigotes with IC values of 32.0 and 6.7 μM, respectively, while flavonoid 2 was inactive. Isolated flavonoids 1-3 were also tested in mammalian fibroblasts and showed CC values of 24.8, 48.7 and 153.1 μM, respectively. Chemically, these results suggested that the free aglycone plays an important role in the bioactivity while the presence of p-coumaroyl unities linked in the rhamnoside unity is important to enhance the antitrypanosomal activity and reduce the mammalian cytotoxicity. The mechanism of cellular death was investigated for the most potent flavonoid 3 in the trypomastigotes using fluorescent and luminescent-based assays. It indicated that this compound induced neither permeabilization of the plasma membrane nor depolarization of the membrane electric potential. However, early time incubation (20 min) with flavonoid 3 resulted in a constant elevation of the Ca levels inside the parasite. This effect was followed by a mitochondrial imbalance, leading to a hyperpolarization and depolarization of the mitochondrial membrane potential, with reduction of the ATP levels. During this time, the levels of reactive oxygen species levels (ROS) were unaltered. The leakage of Ca from the intracellular pools can affect the bioenergetics system of T. cruzi, leading to the parasite death. Therefore, flavonoid 3 can be a useful tool for future studies against T. cruzi parasites.
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http://dx.doi.org/10.1016/j.cbi.2021.109661DOI Listing
September 2021

Metabolomics reveals biomarkers in human urine and plasma to predict cytochrome P450 2D6 (CYP2D6) activity.

Br J Pharmacol 2021 Aug 7. Epub 2021 Aug 7.

Division of Clinical Pharmacology and Toxicology, Geneva University Hospitals, Geneva, Switzerland.

Background And Purpose: Individualized assessment of cytochrome P450 2D6 (CYP2D6) activity is usually performed through phenotyping following administration of a probe drug to measure the enzyme's activity. To avoid any iatrogenic harm (allergic drug reaction, dosing error) related to the probe drug, the development of non-burdensome tools for real-time phenotyping of CYP2D6 could significantly contribute to precision medicine. This study focuses on the identification of markers of the CYP2D6 enzyme in human biofluids using an LC-high-resolution mass spectrometry-based metabolomic approach.

Experimental Approach: Plasma and urine samples from healthy volunteers were analysed before and after intake of a daily dose of paroxetine 20 mg over 7 days. CYP2D6 genotyping and phenotyping, using single oral dose of dextromethorphan 5 mg, were also performed in all participants.

Key Results: We report four metabolites of solanidine and two unknown compounds as possible novel CYP2D6 markers. Mean relative intensities of these features were significantly reduced during the inhibition session compared with the control session (n = 37). Semi-quantitative analysis showed that the largest decrease (-85%) was observed for the ion m/z 432.3108 normalized to solanidine (m/z 398.3417). Mean relative intensities of these ions were significantly higher in the CYP2D6 normal-ultrarapid metabolizer group (n = 37) compared with the poor metabolizer group (n = 6). Solanidine intensity was more than 15 times higher in CYP2D6-deficient individuals compared with other volunteers.

Conclusion And Implications: The applied untargeted metabolomic strategy identified potential novel markers capable of semi-quantitatively predicting CYP2D6 activity, a promising discovery for personalized medicine.
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http://dx.doi.org/10.1111/bph.15651DOI Listing
August 2021

Identification of Potential Antiseizure Agents in using Zebrafish and Mouse Epilepsy Models.

ACS Chem Neurosci 2021 05 29;12(10):1791-1801. Epub 2021 Apr 29.

School of Pharmaceutical Sciences, University of Geneva, CMU-Rue Michel-Servet 1, CH-1211 Geneva 4, Switzerland.

The resin of the tree Flueck. (synonym: ; Burseraceae), also known as "frankincense", is a traditional remedy used for central nervous system disorders in East Africa. Here we report the evaluation of its antiseizure activity in zebrafish and mouse epilepsy models to identify novel antiseizure compounds. The resin was extracted by solvents of increasing polarity. The hexane extract demonstrated the strongest antiseizure activity and was therefore subjected to bioactivity-guided isolation, which leaded to the isolation of eight terpene derivatives. A new prenylbicyclogermacrene derivative () was isolated along with seven other compounds (, -). Among them, the triterpene β-boswellic acid () showed the strongest activity and reduced 90% of pentylenetetrazole (PTZ)-induced seizures at 100 μg/mL. In parallel to , a commercial extract of was also evaluated and showed moderate bioactivity (45% reduction at 30 μg/mL). The extract of was subjected to targeted isolation of other boswellic acid derivatives (-), which were evaluated for antiseizure activity in comparison with . In the whole series, β-boswellic acid () was the most active (60% reduction at 200 μM), and its potency was also confirmed with its purchased standard (). Pure nanoparticles of and a commercially formulated extract of were tested in a PTZ-kindling mouse seizure model. This notably revealed that the administration reduced seizures by 50% in this mouse model, which was consistent with its detection and quantification in plasma and brain samples. This study and the preclinical evaluation performed indicate that β-boswellic acid, common to various species of , has some potential as an antiseizure agent.
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http://dx.doi.org/10.1021/acschemneuro.1c00044DOI Listing
May 2021

Metabolite profile of Nectandra oppositifolia Nees & Mart. and assessment of antitrypanosomal activity of bioactive compounds through efficiency analyses.

PLoS One 2021 25;16(2):e0247334. Epub 2021 Feb 25.

Center of Natural Sciences and Humanities, Federal University of ABC, Santo Andre, Sao Paulo, Brazil.

EtOH extracts from the leaves and twigs of Nectandra oppositifolia Nees & Mart. shown activity against amastigote forms of Trypanosoma cruzi. These extracts were subjected to successive liquid-liquid partitioning to afford bioactive CH2Cl2 fractions. UHPLC-TOF-HRMS/MS and molecular networking were used to obtain an overview of the phytochemical composition of these active fractions. Aiming to isolate the active compounds, both CH2Cl2 fractions were subjected to fractionation using medium pressure chromatography combined with semi-preparative HPLC-UV. Using this approach, twelve compounds (1-12) were isolated and identified by NMR and HRMS analysis. Several isolated compounds displayed activity against the amastigote forms of T. cruzi, especially ethyl protocatechuate (7) with EC50 value of 18.1 μM, similar to positive control benznidazole (18.7 μM). Considering the potential of compound 7, protocatechuic acid and its respective methyl (7a), n-propyl (7b), n-butyl (7c), n-pentyl (7d), and n-hexyl (7e) esters were tested. Regarding antitrypanosomal activity, protocatechuic acid and compound 7a were inactive, while 7b-7e exhibited EC50 values from 20.4 to 11.7 μM, without cytotoxicity to mammalian cells. These results suggest that lipophilicity and molecular complexity play an important role in the activity while efficiency analysis indicates that the natural compound 7 is a promising prototype for further modifications to obtain compounds effective against the intracellular forms of T. cruzi.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0247334PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7906415PMC
August 2021

Production of Highly Active Antiparasitic Compounds from the Controlled Halogenation of the Crude Plant Extract.

J Nat Prod 2020 09 9;83(9):2631-2640. Epub 2020 Sep 9.

School of Pharmaceutical Sciences and Institute of Pharmaceutical Sciences of Western Switzerland (ISPSW), University of Geneva, CMU, Rue Michel Servet 1, 1211 Geneva 4, Switzerland.

Direct halogenation of phenolic compounds present in the CHCl extract of the roots of was investigated to enhance chemodiversity. The approach is based on eco-friendly reactions using NaBr, NaI, and NaCl in aqueous media to generate multiple "unnatural" halogenated natural products from crude extracts. The halogenation reactions, monitored by UHPLC-PDA-ELSD-MS, were optimized to generate mono-, di-, or trihalogenated derivatives. To isolate these compounds, the reactions were scaled up and the halogenated analogues were isolated by semipreparative HPLC-UV and fully characterized by NMR and HR-MS data. All of the original 16 halogenated derivatives were evaluated for their antiparasitic activities against the parasites and . Compounds presenting selective antiparasitic activities against one or both parasites with IC values comparable to the reference were identified.
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http://dx.doi.org/10.1021/acs.jnatprod.0c00433DOI Listing
September 2020

Generation of Stilbene Antimicrobials against Multiresistant Strains of through Biotransformation by the Enzymatic Secretome of .

J Nat Prod 2020 08 24;83(8):2347-2356. Epub 2020 Jul 24.

School of Pharmaceutical Sciences, University of Geneva, CMU, Rue Michel Servet 1, 1211 Geneva 4, Switzerland.

The biotransformation of a mixture of resveratrol and pterostilbene was performed by the protein secretome of Several reaction conditions were tested to overcome solubility issues and to improve enzymatic activity. Using MeOH as cosolvent, a series of unusual methoxylated compounds was generated. The reaction was scaled-up, and the resulting mixture purified by semipreparative HPLC-PDA-ELSD-MS. Using this approach, 15 analogues were isolated in one step. Upon full characterization by NMR and HRMS analyses, eight of the compounds were new. The antibacterial activities of the isolated compounds were evaluated in vitro against the opportunistic pathogens and . The selectivity index was calculated based on cytotoxic assays performed against human liver carcinoma cells (HepG2) and the human breast epithelial cell line (MCF10A). Some compounds revealed remarkable antibacterial activity against multidrug-resistant strains of with moderate human cell line cytotoxicity.
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http://dx.doi.org/10.1021/acs.jnatprod.0c00071DOI Listing
August 2020

Zebrafish-based identification of the antiseizure nucleoside inosine from the marine diatom Skeletonema marinoi.

PLoS One 2018 24;13(4):e0196195. Epub 2018 Apr 24.

Luxembourg Centre for Systems Biomedicine, Université du Luxembourg, Belvaux, Luxembourg.

With the goal of identifying neuroactive secondary metabolites from microalgae, a microscale in vivo zebrafish bioassay for antiseizure activity was used to evaluate bioactivities of the diatom Skeletonema marinoi, which was recently revealed as being a promising source of drug-like small molecules. A freeze-dried culture of S. marinoi was extracted by solvents with increasing polarities (hexane, dichloromethane, methanol and water) and these extracts were screened for anticonvulsant activity using a larval zebrafish epilepsy model with seizures induced by the GABAA antagonist pentylenetetrazole. The methanolic extract of S. marinoi exhibited significant anticonvulsant activity and was chosen for bioassay-guided fractionation, which associated the bioactivity with minor constituents. The key anticonvulsant constituent was identified as the nucleoside inosine, a well-known adenosine receptor agonist with previously reported antiseizure activities in mice and rat epilepsy models, but not reported to date as a bioactive constituent of microalgae. In addition, a UHPLC-HRMS metabolite profiling was used for dereplication of the other constituents of S. marinoi. Structures of the isolated compounds were elucidated by nuclear magnetic resonance and high-resolution spectrometry. These results highlight the potential of zebrafish-based screening and bioassay-guided fractionation to identify neuroactive marine natural products.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0196195PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5916873PMC
July 2018

Structural design, synthesis and substituent effect of hydrazone-N-acylhydrazones reveal potent immunomodulatory agents.

Bioorg Med Chem 2018 05 25;26(8):1971-1985. Epub 2018 Feb 25.

FIOCRUZ, Instituto Gonçalo Moniz, 40296-710 Salvador, BA, Brazil; Centro de Biotecnologia e Terapia Celular, Hospital São Rafael, 41253-190 Salvador, BA, Brazil. Electronic address:

4-(Nitrophenyl)hydrazone derivatives of N-acylhydrazone were synthesized and screened for suppress lymphocyte proliferation and nitrite inhibition in macrophages. Compared to an unsubstituted N-acylhydrazone, active compounds were identified within initial series when hydroxyl, chloride and nitro substituents were employed. Structure-activity relationship was further developed by varying the position of these substituents as well as attaching structurally-related substituents. Changing substituent position revealed a more promising compound series of anti-inflammatory agents. In contrast, an N-methyl group appended to the 4-(nitrophenyl)hydrazone moiety reduced activity. Anti-inflammatory activity of compounds is achieved by modulating IL-1β secretion and prostaglandin E2 synthesis in macrophages and by inhibiting calcineurin phosphatase activity in lymphocytes. Compound SintMed65 was advanced into an acute model of peritonitis in mice, where it inhibited the neutrophil infiltration after being orally administered. In summary, we demonstrated in great details the structural requirements and the underlying mechanism for anti-inflammatory activity of a new family of hydrazone-N-acylhydrazone, which may represent a valuable medicinal chemistry direction for the anti-inflammatory drug development in general.
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http://dx.doi.org/10.1016/j.bmc.2018.02.047DOI Listing
May 2018

Unguiculin A and Ptilomycalins E-H, Antimalarial Guanidine Alkaloids from the Marine Sponge Monanchora unguiculata.

J Nat Prod 2017 05 3;80(5):1404-1410. Epub 2017 Apr 3.

Laboratoire de Chimie des Substances Naturelles et des Sciences des Aliments, Faculté des Sciences et Technologies, Université de La Réunion , 15 Avenue René Cassin, CS 92003, 97744 Saint-Denis Cedex 9, La Réunion, France.

Chemical study of the CHCl-MeOH (1:1) extract from the sponge Monanchora unguiculata collected in Madagascar highlighted five new compounds, one acyclic guanidine alkaloid, unguiculin A (1) and four pentacyclic alkaloids, ptilomycalins E-H (2-5), along with four known compounds: crambescidin 800 (6) and crambescidin 359 (7), crambescidic acid (8), and fromiamycalin (9). Their structures were elucidated by 1D and 2D NMR spectra and HRESIMS data. All compounds were evaluated for their cytotoxicity against KB cells and their antiplasmodial activity. The new ptilomycalin E (2) and the mixture of the new ptilomycalins G (4) and H (5) showed promising cytotoxicity against KB cells with IC values of 0.85 and 0.92 μM, respectively. Ptilomycalin F (3) and fromiamycalin (9) exhibited promising activity against Plasmodium falciparum with IC values of 0.23 and 0.24 μM, respectively.
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http://dx.doi.org/10.1021/acs.jnatprod.6b01079DOI Listing
May 2017

Anti-Candida Cassane-Type Diterpenoids from the Root Bark of Swartzia simplex.

J Nat Prod 2015 Dec 11;78(12):2994-3004. Epub 2015 Dec 11.

School of Pharmaceutical Sciences, EPGL, University of Geneva, University of Lausanne , 30 quai Ernest-Ansermet, CH-1211 Geneva 4, Switzerland.

A dichloromethane extract of the roots from the Panamanian plant Swartzia simplex exhibited a strong antifungal activity in a bioautography assay against a genetically modified hypersusceptible strain of Candida albicans. At-line HPLC activity based profiling of the crude extract enabled a precise localization of the antifungal compounds, and dereplication by UHPLC-HRESIMS indicated the presence of potentially new metabolites. Transposition of the HPLC reversed-phase analytical conditions to medium-pressure liquid chromatography (MPLC) allowed an efficient isolation of the major constituents. Minor compounds of interest were isolated from the MPLC fractions using semipreparative HPLC. Using this strategy, 14 diterpenes (1-14) were isolated, with seven (5-10, 14) being new antifungal natural products. The new structures were elucidated using NMR spectroscopy and HRESIMS analysis. The absolute configurations of some of the compounds were elucidated by electronic circular dichroism spectroscopy. The antifungal properties of these compounds were evaluated as their minimum inhibitory concentrations in a dilution assay against both hypersusceptible and wild-type strains of C. albicans and by assessment of their antibiofilm activities. The potential cytological effects on the ultrastructure of C. albicans of the antifungal compounds isolated were evaluated on thin sections by transmission electron microscopy.
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http://dx.doi.org/10.1021/acs.jnatprod.5b00744DOI Listing
December 2015

Zebrafish bioassay-guided microfractionation identifies anticonvulsant steroid glycosides from the Philippine medicinal plant Solanum torvum.

ACS Chem Neurosci 2014 Oct 8;5(10):993-1004. Epub 2014 Sep 8.

School of Pharmaceutical Sciences, University of Geneva, University of Lausanne , 30, quai Ernest-Ansermet, CH-1211 Geneva 4, Switzerland.

Medicinal plants used for the treatment of epilepsy are potentially a valuable source of novel antiepileptic small molecules. To identify anticonvulsant secondary metabolites, we performed an in vivo, zebrafish-based screen of medicinal plants used in Southeast Asia for the treatment of seizures. Solanum torvum Sw. (Solanaceae) was identified as having significant anticonvulsant activity in zebrafish larvae with seizures induced by the GABAA antagonist pentylenetetrazol (PTZ). This finding correlates well with the ethnomedical use of this plant in the Philippines, where a water decoction of S. torvum leaves is used to treat epileptic seizures. HPLC microfractionation of the bioactive crude extract, in combination with the in vivo zebrafish seizure assay, enabled the rapid localization of several bioactive compounds that were partially identified online by UHPLC-TOF-MS as steroid glycosides. Targeted isolation of the active constituents from the methanolic extract enabled the complete de novo structure identification of the six main bioactive compounds that were also present in the traditional preparation. To partially mimic the in vivo metabolism of these triterpene glycosides, their common aglycone was generated by acid hydrolysis. The isolated molecules exhibited significant anticonvulsant activity in zebrafish seizure assays. These results underscore the potential of zebrafish bioassay-guided microfractionation to rapidly identify novel bioactive small molecules of natural origin.
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http://dx.doi.org/10.1021/cn5001342DOI Listing
October 2014

Vitis vinifera canes, a new source of antifungal compounds against Plasmopara viticola, Erysiphe necator, and Botrytis cinerea.

J Agric Food Chem 2013 Jun 3;61(23):5459-67. Epub 2013 Jun 3.

Swiss Federal Research Station Agroscope Changins Wädenswil ACW, Route de Duiller 50, PO Box 1012, 1260 Nyon, Switzerland.

Methanolic and ethanolic crude extracts of Vitis vinifera canes exhibited significant antifungal activity against the three major fungal pathogens affecting grapevines, Plasmopara viticola, Erysiphe necator and Botrytis cinerea. The active extracts were analyzed by LC-PDA-ESI-MS, and selected compounds were identified. Efficient targeted isolation using medium-pressure liquid chromatography afforded six pure constituents in one step. The structures of the isolated compounds were elucidated by NMR and HRMS. Six identified compounds (ampelopsin A, hopeaphenol, trans-resveratrol, ampelopsin H, ε-viniferin, and E-vitisin B) presented antifungal activities against P. viticola. ε-Viniferin also exhibited a low antifungal activity against B. cinerea. None of the identified compounds inhibited the germination of E. necator. The potential to develop a novel natural fungicide against the three major fungal pathogens affecting V. vinifera from viticulture waste material is discussed.
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http://dx.doi.org/10.1021/jf4010252DOI Listing
June 2013

Hypotensive activity of an n-butanol extract and their purified compounds from leaves of Phyllanthus acidus (L.) Skeels in rats.

Eur J Pharmacol 2010 Dec 21;649(1-3):301-13. Epub 2010 Sep 21.

Department of Physiology, Faculty of Science, Prince of Songkla University, Hat-Yai, 90112, Thailand.

We aimed to investigate the effects, identify the active substances and establish the mechanisms involved in the hypotensive activity of an n-butanol extract from leaves of Phyllanthus acidus (PA extract). PA extract caused a decrease in blood pressure of anesthetized rats that was not modified by atropine or propranolol. PA extract caused a persistent dilatation of thoracic aortic rings preconstricted with either phenylephrine or KCl, and these effects were not modified by LNA or removal of the vascular endothelium. For phenylephrine-preconstricted aortic rings, the dilatory activity of the PA extract was not modified by atropine, propranolol or indomethacin. TEA, glybenclamide or ODQ significantly inhibited the dilatory activity of the PA extract on endothelium-denuded aortic rings. Nifedipine or a Ca(2+)-free medium depressed the aortic rings constrictor response to phenylephrine, and that was further augmented by the PA extract. Adenosine, 4-hydroxybenzoic acid, caffeic acid, hypogallic acid, and kaempferol were isolated from the PA extract. Each caused a decrease in blood pressure and dilatation of the aortic rings. LNA or removal of the endothelium reduced this activity. ODQ and TEA attenuated the vasodilatory activity of adenosine whereas glybenclamide and ODQ attenuated the effect of hypogallic acid. These results suggest that the hypotensive activities of the PA extract is likely the result of the direct action of these five compounds on the blood vessels by stimulating release of nitric oxide from the vascular endothelium, in part through stimulation of soluble guanylate cyclase, and opening of K(ATP) and K(Ca) channels in the vascular smooth muscle.
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http://dx.doi.org/10.1016/j.ejphar.2010.09.038DOI Listing
December 2010

Two new tropane alkaloids from the bark of Erythroxylum vacciniifolium Mart. (Erythroxylaceae).

Nat Prod Commun 2009 Oct;4(10):1337-40

Department of Research and Development, Aché Laboratórios Farmacêuticos S.A. Rodovia Presidente Dutra, km 222,2. Guarulhos-SP, cep 07034-904, Brazil.

Two new tropane alkaloid N-oxides substituted by a methylpyrrole moiety were isolated from the bark of Erythroxylum vacciniifolium Mart. (Erythroxylaceae), a Brazilian indigenous plant, locally known as catuaba and used in traditional medicine as an aphrodisiac. The alkaloid structures were determined by a combination of high resolution mass spectrometry and multi-dimensional NMR spectroscopy.
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October 2009

On-line identification of phenolic compounds of Trifolium species using HPLC-UV-MS and post-column UV-derivatisation.

Phytochem Anal 2007 Jan-Feb;18(1):13-23

Laboratory of Phamacognosie and Phytochemistry, School of Pharmaceutical Sciences, University of Geneva, University of Lausanne, 30 quai Ernest-Ansermet-CH-1211 Geneva 4, Switzerland.

In an ongoing search for new active compounds in the field of phytoestrogens, a simple HPLC-UV-MS method has been developed in order to identify phenolic compounds. The study was performed on three different species of Trifolium (Leguminosae), namely Trifolium pratense L., T. pallescens Schreb. and T. alpinum L, collected in Switzerland. The comparison between the dichloromethane extracts revealed that the main aglycones are present in the three species whereas the methanolic extracts show different glycosides and malonate derivatives. The compounds of interest were mainly flavonoids, isoflavonoids and clovamides. Their identities were confirmed from retention times, UV and MS analyses and UV shifts following post-column derivatisation.
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http://dx.doi.org/10.1002/pca.946DOI Listing
February 2007

On-line identification of further flavone C- and O-glycosides from sugarcane (Saccharum officinarum L., Gramineae) by HPLC-UV-MS.

Phytochem Anal 2006 Sep-Oct;17(5):337-43

Universidade de São Paulo, Instituto de Química de São Carlos, Brazil.

HPLC-UV-MS (APCI-MS/MS and CID/MS) was utilised for the identification of eight additional flavone glycosides from sugarcane (Saccharum officinarum L., Gramineae) extracts of bagasse, leaves and juice ('garapa'). Relevant information about substitution patterns was obtained through UV detection using post-column addition of shift reagents, while tandem MS provided structural information confirming the proposed structures of the C-glycosides vitexin, orientin, luteolin-8-C-(rhamnosylglucoside), 4',5'-dimethyl-luteolin-8-C-glycoside and the isomeric pair schaftoside-isoschaftoside, besides the O-glycosides tricin-7-O-neohesperidoside and tricin-7-O-glycoside.
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http://dx.doi.org/10.1002/pca.923DOI Listing
December 2006

New and bioactive aromatic compounds from Zanthoxylum zanthoxyloides.

Planta Med 2006 Jun 19;72(8):746-50. Epub 2006 Jun 19.

Laboratoire de Pharmacognosie et Phytochimie, Ecole de Pharmacie Genève-Lausanne, Université de Genève, Genève, Switzerland.

In the course of a study of medicinal plants from Mali, the root bark of Zanthoxylum zanthoxyloides Lam. (Rutaceae) was investigated. The root bark of this plant is used as a toothbrush by West African people. Phytochemical investigation of the MeOH extract of Zanthoxylum zanthoxyloides Lam. (Rutaceae) led to the isolation of different biologically active compounds. The separation of acetylcholinesterase inhibitors was performed by centrifugal partition chromatography (CPC). The fractions were monitored by direct TLC bioautographic assays. The bio-guided isolation led to the isolation of a new peroxide derivative. In addition, LC/UV/MS analysis performed on the crude MeOH extract allowed on-line identification of some known compounds. The structures of the isolated compounds were elucidated by classical spectroscopic methods including UV, NMR, MS and HR-MS.
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http://dx.doi.org/10.1055/s-2006-941504DOI Listing
June 2006

Isolation and on-line identification of antioxidant compounds from three Baccharis species by HPLC-UV-MS/MS with post-column derivatisation.

Phytochem Anal 2005 Sep-Oct;16(5):307-14

Programa de Pós-graduação em Ciências Farmacêuticas, Universidade Federal do Rio Grande do Sul, Porto Alegre-RS, Brazil.

The aqueous extracts of aerial parts of Baccharis trimera (Less.) DC., B. crispa Spreng. and B. usterii Heering (Asteraceae) displayed significant radical scavenging activity in a diphenylpicrylhydrazole (DPPH)/TLC assay. In order to rapidly identify the active principles, the crude extracts were analysed by HPLC-UV, and an HPLC-micro-fractionation of the extract of B. usterii was performed. Six quinic acids derivatives (1-6) were isolated from B. usterii by MPLC. The fractions were monitored by DPPH/TLC assay and a series of radical-scavenging quinic acid derivatives could be identified. The comparison of the HPLC profiles of the extracts of B. usterii, B. trimera and B. crispa was performed. In order to obtain complementary on-line structural information for all peaks of interest, HPLC-MS/MS together with HPLC-UV involving post-column addition of UV shift reagents was undertaken on the crude extract. The interpretation of these data permitted the on-line identification of known compounds, some of which are reported for the first time in this plant.
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http://dx.doi.org/10.1002/pca.826DOI Listing
December 2005

Methylpyrrole tropane alkaloids from the bark of Erythroxylum vacciniifolium.

J Nat Prod 2005 Aug;68(8):1153-8

Laboratory of Pharmacognosy and Phytochemistry, University of Geneva, CH-1211 Geneva 4, Switzerland.

Nine new tropane alkaloids substituted by a methylpyrrole moiety were isolated from the bark of Erythroxylum vacciniifolium, a Brazilian endemic plant used in traditional medicine and locally known as catuaba. All compounds were elucidated as tropanediol or -triol alkaloids esterified by at least one 1-methyl-1H-pyrrole-2-carboxylic acid. One of the isolated compounds was identified as a tropane alkaloid N-oxide. Their structures were determined by high-resolution mass spectrometry and multidimensional NMR spectroscopy.
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http://dx.doi.org/10.1021/np040144hDOI Listing
August 2005

Phytochemistry in the microgram domain - a LC-NMR perspective.

Magn Reson Chem 2005 Sep;43(9):697-709

Laboratoire de Pharmacognosie et Phytochimie, Ecole de Pharmacie Genève-Lausanne, Section des Sciences Pharmaceutiques, Université de Genève, Switzerland.

Plants represent an extraordinary reservoir of novel molecules and there is currently a resurgence of interest in the vegetable kingdom as a possible source of new lead compounds for introduction into therapeutical screening programs. In order to discover potential new bioactive natural products, the dereplication of crude plant extracts performed prior to isolation work is of crucial importance for avoiding the isolation of a known constituent. In this respect, chemical screening strategies have been developed using hyphenated techniques (LC/UV-DAD, LC-MS and LC-NMR). In our laboratory, these techniques have been fully integrated into the isolation process and are used for the chemical screening of crude plant extracts in complement with on-line or at-line bioassays. LC-UV-MS is used as a first dereplication step in combination with UV and MS databases, while LC-NMR is performed in a second step for de novo on-line structure determination. This approach enables the partial or the complete on-line identification of natural products in complex matrices such as crude plant extracts. These methods also give a unique possibility to study unstable compounds, which rapidly degrade or which are not separable at a preparative level. In the multi-hyphenated approach used (hypernation), LC-NMR plays a key role since it provides the most detailed structural information. The relatively low sensitivity of this technique, however, requires that strategies for high loading of plant extracts are developed and compromises for solvent selection have to be made. For more demanding experiments, at-line strategies based on the microfractionation of the LC-peak of interest and recording of spectra in fully deuterated solvents in microflow probes represent a promising alternative.
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http://dx.doi.org/10.1002/mrc.1631DOI Listing
September 2005

Flavonoids from the stem of Eriophorum scheuchzeri.

J Nat Prod 2005 Jul;68(7):1094-8

Laboratoire de Pharmacognosie et Phytochimie, Section de Sciences Pharmaceutiques, University of Geneva, CH-1211 Geneva, Switzerland.

Activity-guided isolation of antifungal, antibacterial, and antioxidant compounds from the dichloromethane extract of the aerial parts of Eriophorum scheuchzeri led to the isolation of eight flavonoids. Three isoflavones and one flavanone are new natural compounds. The isolation of the bioactive compounds was performed by centrifugal partition chromatography. Fractions and pure compounds were monitored by a direct TLC bioautographic assay. Their structures were elucidated by spectroscopic and chemical methods.
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http://dx.doi.org/10.1021/np0580107DOI Listing
July 2005

On-line identification of sugarcane (Saccharum officinarum L.) methoxyflavones by liquid chromatography-UV detection using post-column derivatization and liquid chromatography-mass spectrometry.

J Chromatogr A 2005 Jul;1082(1):51-9

Instituto de Química de São Carlos, Universidade de São Paulo, Caixa Postal 780, 13560-970 São Carlos, SP, Brazil.

Sugarcane (Saccharum officinarum L., Gramineae) bagasse and leaves were investigated for their flavonoid content and transgenic sugarcane ("Bowman-Birk" and "Kunitz") was compared with non-modified ("control") plants. Analyses were carried out by high-performance liquid chromatography coupled to diode array UV detection (LC/UV), also using post-column addition of shift reagents, and tandem MS (atmospheric pressure chemical ionization-MS/MS and collision-induced dissociation-MS). On-line UV and MS data demonstrated the presence of methoxyflavone glycosides and aglycones in a total of seven compounds. Three naturally occurring flavones glycosides and two unusual erythro- and threo-diastereoisomeric flavolignan 7-O-glucosides were identified together with their aglycones.
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http://dx.doi.org/10.1016/j.chroma.2005.01.083DOI Listing
July 2005

On-line characterisation of apple polyphenols by liquid chromatography coupled with mass spectrometry and ultraviolet absorbance detection.

J Chromatogr A 2004 Aug;1046(1-2):89-100

Departamento de Química Analítica, Facultad de Ciencias, Universidad del País Vasco/Euskal Herriko Unibertsitatea E-48080 Bilbao, Spain.

Apple polyphenols were characterised by means of hyphenated techniques such as HPLC coupled to UV photodiode array detection (LC-DAD) and to mass spectrometry (LC-MS). LC-MS using atmospheric pressure ionisation (APCI) in the positive ion mode provided the molecular weight, the number of hydroxyl groups, the number of sugars and an idea about the substitution pattern of the polyphenols. LC-DAD with postcolumn addition of UV shift reagents afforded precise structural information about the position of the free hydroxyl groups in the polyphenolic nucleus. Five isorhamnetin glycosides, two hydroxyphloretin glycosides and quercetin were reported in apple peel for the first time. Postcolumn addition of UV shift reagents in LC-DAD analysis confirmed the presence of isorhamnetin glycosides and not the isomeric glycosides of rhamnetin. Moreover, isorhamnetin-3-O-rhamnoglucoside was identified unambiguously by comparison with a standard. These results are relevant not only from a chemotaxonomic point of view, but also in the control of authenticity of fruit derived products in order to detect fraudulent admixtures.
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August 2004

Two unusual acetogenins from the roots of Annona salzmanii.

J Nat Prod 2003 Jun;66(6):755-8

Laboratoire de Pharmacognosie, CNRS UPRES-A 8076 (BIOCIS), Faculté de Pharmacie, 92296 Châtenay-Malabry, France.

Two new acetogenins, parisin (1) and salzmanolin (2), were isolated from a MeOH extract of the roots of Annona salzmanii. The structures of 1 and 2 were elucidated by spectroscopic methods including LSI-MS/MS, on both the natural compounds and their acetonide derivatives (1a and 2a). Compounds 1 and 2 showed significant activity against the KB and Vero cell lines.
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http://dx.doi.org/10.1021/np020543hDOI Listing
June 2003

New dihydroalkylhexenones from Lannea edulis.

J Nat Prod 2003 Apr;66(4):578-80

Institute of Pharmacognosy and Phytochemistry, University of Lausanne, BEP, CH-1015 Lausanne, Switzerland.

Activity-guided isolation of radical-scavenging compounds from the dichloromethane extract of the root bark of Lannea edulis led to isolation of two known bioactive alkylphenols [cardonol 7 (1) and cardonol 13 (2)], and three new dihydroalkylhexenones were also isolated (3-5). Their structures were elucidated by spectroscopic and chemical methods. The absolute configuration of 4 was determined by the Mosher ester method.
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http://dx.doi.org/10.1021/np0202428DOI Listing
April 2003

Tropane alkaloids from the bark of Erythroxylum vacciniifolium.

J Nat Prod 2003 Apr;66(4):497-502

Institut de Pharmacognosie et Phytochimie, Université de Lausanne, BEP, CH-1015 Lausanne, Switzerland.

Eight new tropane alkaloids (1-8) were isolated from the bark of "catuaba", a Brazilian endemic plant Erythroxylum vacciniifolium Martius. Their structures were determined by high-resolution mass spectrometry and multidimensional NMR spectroscopy.
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http://dx.doi.org/10.1021/np020512mDOI Listing
April 2003

Antifungal and antioxidant compounds from the root bark of Fagara zanthoxyloides.

Planta Med 2003 Apr;69(4):316-20

Institut de Pharmacognosie et Phytochimie, Université de Lausanne, Lausanne, Switzerland.

Phytochemical investigation of the CH 2 Cl 2 extract of Fagara zanthoxyloides Lam. (Rutaceae) led to the isolation of eleven compounds. One phenylethanoid derivative is a new natural product. The isolation of the antifungal and the antioxidant compounds was monitored by direct TLC bioautographic assays. The structures of the isolated compounds were elucidated by classical spectroscopic methods including UV, NMR, MS and HR-MS.
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http://dx.doi.org/10.1055/s-2003-38877DOI Listing
April 2003

Absolute configuration of a tetrahydrophenanthrene from Heliotropium ovalifolium by LC-NMR of its Mosher esters.

J Nat Prod 2003 Jan;66(1):17-20

Institut de Pharmacognosie et Phytochimie, Université de Lausanne, BEP, CH-1015 Lausanne, Switzerland.

A new tetrahydrophenanthrene (1, (1R,2R)-1-hydroxy-2-methoxy-6,9-dimethyl-2,3-dihydrophenanthren-4(1H)-one (heliophenanthrone)) has been isolated from the aerial parts of Heliotropium ovalifolium. Its structure was elucidated on the basis of spectroscopic data, and the absolute configuration of the asymmetric centers was determined from LC-NMR data of the Mosher ester derivatives.
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http://dx.doi.org/10.1021/np020366kDOI Listing
January 2003

Prenylated isoflavonoids from the root bark of Erythrina vogelii.

J Nat Prod 2002 Mar;65(3):403-6

Institut de Pharmacognosie et Phytochimie, Université de Lausanne, BEP, CH-1015 Lausanne, Switzerland.

Four new prenylated isoflavonoids, vogelins D-G (1-4), were isolated from the CH2Cl2 extract of Erythrina vogelii root bark in addition to the known compounds isolupalbigenin (5), ficuisoflavone (6), ulexone (7), isochandalon (8), and isoderrone (9). The structures 1-4 were elucidated by spectroscopic and chemical methods. The absolute configuration of compound 1 was determined on the basis of its CD spectrum. Possible biogenetic relationships among the E. vogelii isoflavonoids are briefly discussed.
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http://dx.doi.org/10.1021/np0103867DOI Listing
March 2002
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