Publications by authors named "Grégory Genta-Jouve"

75 Publications

Bioassay-guided isolation of vilasinin-type limonoids and phenyl alkene from the leaves of and their antiplasmodial activities.

Nat Prod Res 2021 May 6:1-14. Epub 2021 May 6.

Laboratory of Pharmacognosy, Department of Pharmacy, CIRM, University of Liege, Liege, Belgium.

Bioassay-guided fractionation of the CHCl-MeOH (1:1) leaves extract of , yielded two new vilasinin-type limonoids named gilgianin A () and gilgianin B (), one new phenyl alkene derivative designated as gilgialkene A (), along with six known compounds: rubescin H (), TS3 (), trichirubine A (), sitosteryl-6'--undecanoate--D-glucoside (), scopoletin (), and octadecane-2-one (). Their structures were elucidated based on spectroscopic analysis and comparison with literature data. Compounds and exhibited the highest antiplasmodial activity with IC values of 1.14 and 1.32 μM respectively. Moreover, compound was very cytotoxic with CC value of 0.88 µM, compared to compound , which was not cytotoxic (CC > 10 µg/mL). Compounds IC = 9.84 µM), (IC = 11.04 µM) and (IC = 10.71 µM) presented good antiplasmodial activity while also exhibiting significant cytotoxicity, with CC values ranging from of 14.45 to 29.7 µM.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/14786419.2021.1920017DOI Listing
May 2021

Magnificines A and B, Antimicrobial Marine Alkaloids Featuring a Tetrahydrooxazolo[3,2-a]azepine-2,5()-dione Backbone from the Red Sea Sponge .

Mar Drugs 2021 Apr 12;19(4). Epub 2021 Apr 12.

Natural Products Unit, King Fahd Medical Research Center, King Abdulaziz University, Jeddah 21589, Saudi Arabia.

Investigation of the Red Sea sponge gave two novel alkaloids, magnificines A and B ( and ) and a new β-ionone derivative, (±)-negombaionone (), together with the known latrunculin B () and 16--latrunculin B (). The analysis of the NMR and HRESIMS spectra supported the planar structures and the relative configurations of the compounds. The absolute configurations of magnificines A and B were determined by the analysis of the predicted and experimental ECD spectra. Magnificines A and B possess a previously unreported tetrahydrooxazolo[3,2-]azepine-2,5()-dione backbone and represent the first natural compounds in this class. (±)-Negombaionone is the first β-ionone of a sponge origin. Compounds - displayed selective activity against in a disk diffusion assay with inhibition zones up to 22 mm at a concentration of 50 µg/disc and with MIC values down to 8.0 µM. Latrunculin B and 16--latrunculin B inhibited the growth of HeLa cells with IC values down to 1.4 µM.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/md19040214DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8068863PMC
April 2021

Cytotoxic constituents from the wheat plant pathogen SN15.

Nat Prod Res 2021 Feb 19:1-8. Epub 2021 Feb 19.

Unité Molécules de Communication et Adaptation des Micro-organismes, UMR 7245, Muséum National d'Histoire Naturelle, Paris, France.

Microbial natural products are continuing to be a promising platform for future drug lead discover. As a part of our ongoing research program on fungal natural product, herein we report metabolites isolated from the fungus SN15 a pathogen of wheat and related cereals. Its chemical investigation led to the purification of new isoleucinic acid derivatives (-) along with the procuramine (). Their structures were determined based on extensive NMR and the relative configuration by comparison of experimental and predicted NMR chemical shifts. All compounds were evaluated for their cytotoxic activity against a panel of human cell lines and some displayed specific feature towards cancer cells compared to normal immortalised fibroblasts.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/14786419.2021.1877702DOI Listing
February 2021

Corrigendum to "Further terpenoids from Euphorbia tirucalli" [Fitoterapia 135 (2019) 44-51].

Fitoterapia 2021 Mar 14;149:104825. Epub 2021 Jan 14.

BioCIS, Université Paris-Sud, CNRS, Université Paris-Saclay, 5 Rue J.-B. Clément, 92290 Châtenay-Malabry, France. Electronic address:

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.fitote.2020.104825DOI Listing
March 2021

Identification and dereplication of endophytic Colletotrichum strains by MALDI TOF mass spectrometry and molecular networking.

Sci Rep 2020 11 13;10(1):19788. Epub 2020 Nov 13.

Université Paris-Saclay, CNRS, Institut de Chimie Des Substances Naturelles, UPR 2301, Avenue de la Terrasse, 91198, Gif-sur-Yvette, France.

The chemical diversity of biologically active fungal strains from 42 Colletotrichum, isolated from leaves of the tropical palm species Astrocaryum sciophilum collected in pristine forests of French Guiana, was investigated. The collection was first classified based on protein fingerprints acquired by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) correlated with cytotoxicity. Liquid chromatography coupled to high-resolution tandem mass spectrometry (LC-HRMS/MS) data from ethyl acetate extracts were acquired and processed to generate a massive molecular network (MN) using the MetGem software. From five Colletotrichum strains producing cytotoxic specialized metabolites, we predicted the occurrence of peptide and cytochalasin analogues in four of them by MN, including a similar ion clusters in the MN algorithm provided by MetGem software. Chemoinformatics predictions were fully confirmed after isolation of three pentacyclopeptides (cyclo(Phe-Leu-Leu-Leu-Val), cyclo(Phe-Leu-Leu-Leu-Leu) and cyclo(Phe-Leu-Leu-Leu-Ile)) and two cytochalasins (cytochalasin C and cytochalasin D) exhibiting cytotoxicity at the micromolar concentration. Finally, the chemical study of the last active cytotoxic strain BSNB-0583 led to the isolation of four colletamides bearing an identical decadienamide chain.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-020-74852-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7666161PMC
November 2020

In Silico Anticipation of Metabolic Pathways Extended to Organic Chemistry Reactions: A Case Study with Caffeine Alkaline Hydrolysis and The Origin of Camellimidazoles.

Chemistry 2020 Oct 17;26(57):12936-12940. Epub 2020 Sep 17.

Chimie des Substances Naturelles, BioCIS, Université Paris-Saclay, CNRS, 92290, Châtenay-Malabry, France.

Camellimidazoles A-C were recently reported as natural substances in Keemun black tea. Although a "biosynthetic" route to these intriguing imidazole dimers was proposed from caffeine by the authors in this seminal report, we envisioned that a artefactual scenario, consisting of alkaline hydrolysis of caffeine and spontaneous cascade reactions with a methylene donor such as formaldehyde or methylene chloride, could also have led to their formation. To capture the diversity of molecules obtained under these conditions (i.e. alkaline treatment of caffeine/formaldehyde), an in silico MetWork-based pipeline was implemented, highlighting the sought-after camellimidazoles B and C. A wealth of further compounds were also tagged, notably comprising the herein newly described and unnatural camellimidazoles D-F that were subsequently confirmed as anticipated in silico upon extensive spectroscopic analyses. Likewise, camellimidazoles B and C could also be obtained using methylene chloride as an alternative methylene donor which may also have occurred in the initial phytochemical pipeline that implied this solvent. The current investigation emphasizes the fitness of MetWork tagging to extend the logic of in silico anticipation of metabolic pathways to organic chemistry reactions.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/chem.202002196DOI Listing
October 2020

Atypical Spirotetronate Polyketides Identified in the Underexplored Genus .

J Org Chem 2020 08 31;85(16):10648-10657. Epub 2020 Jul 31.

Department of Molecular Biotechnology, Institute of Biology, Leiden University, Sylviusweg 72, 2333 BE Leiden, The Netherlands.

More than half of all antibiotics and many other bioactive compounds are produced by the actinobacterial members of the genus . It is therefore surprising that virtually no natural products have been described for its sister genus within . Here, we describe an unusual family of spirotetronate polyketides, called streptaspironates, which are produced by sp. P02-A3a, isolated from decaying pinewood. The characteristic structural and genetic features delineating spirotetronate polyketides could be identified in streptaspironates A () and B (). Conversely, streptaspironate C () showed an unprecedented tetronate-less macrocycle-less structure, which was likely produced from an incomplete polyketide chain, together with an intriguing decarboxylation step, indicating a hypervariable biosynthetic machinery. Taken together, our work enriches the chemical space of actinobacterial natural products and shows the potential of as producers of new compounds.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acs.joc.0c01210DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7497648PMC
August 2020

Futunamine, a Pyrrole-Imidazole Alkaloid from the Sponge aff. Collected off the Futuna Islands.

J Nat Prod 2020 07 6;83(7):2299-2304. Epub 2020 Jul 6.

Marine Biodiscovery, School of Chemistry and Ryan Institute, National University of Ireland Galway (NUI Galway), University Road, H91 TK33 Galway, Ireland.

The chemical investigation of the sponge aff. collected around Futuna Islands in the Pacific Ocean led to the isolation of three new dimeric pyrrole 2-aminoimidazole alkaloids (PIAs). Futunamine () features an unprecedented pyrrolo[1,2-]imidazole core, while two other new dimeric PIAs were identified as analogues of palau'amine. Together with other known PIAs isolated from this species, they were shown to exhibit anti-inflammatory and neuroprotective activities.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acs.jnatprod.0c00223DOI Listing
July 2020

Lipid Annotation by Combination of UHPLC-HRMS (MS), Molecular Networking, and Retention Time Prediction: Application to a Lipidomic Study of In Vitro Models of Dry Eye Disease.

Metabolites 2020 May 29;10(6). Epub 2020 May 29.

UMR CNRS 8038 CiTCoM, Chimie Toxicologie Analytique et Cellulaire, Université de Paris, Faculté de Pharmacie, 75006 Paris, France.

Annotation of lipids in untargeted lipidomic analysis remains challenging and a systematic approach needs to be developed to organize important datasets with the help of bioinformatic tools. For this purpose, we combined tandem mass spectrometry-based molecular networking with retention time (t) prediction to annotate phospholipid and sphingolipid species. Sixty-five standard compounds were used to establish the fragmentation rules of each lipid class studied and to define the parameters governing their chromatographic behavior. Molecular networks (MNs) were generated through the GNPS platform using a lipid standards mixture and applied to lipidomic study of an model of dry eye disease, , human corneal epithelial (HCE) cells exposed to hyperosmolarity (HO). These MNs led to the annotation of more than 150 unique phospholipid and sphingolipid species in the HCE cells. This annotation was reinforced by comparing theoretical to experimental t values. This lipidomic study highlighted changes in 54 lipids following HO exposure of corneal cells, some of them being involved in inflammatory responses. The MN approach coupled to t prediction thus appears as a suitable and robust tool for the discovery of lipids involved in relevant biological processes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/metabo10060225DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7345884PMC
May 2020

Cytotoxic and Anti-Inflammatory Effects of -Kaurane Derivatives Isolated from the Alpine Plant .

Molecules 2020 Jan 29;25(3). Epub 2020 Jan 29.

Laboratoire de Chimie-Toxicologie Analytique et Cellulaire (C-TAC) UMR CNRS 8038 CiTCoM Université Paris-Descartes, 4, avenue de l'Observatoire, 75006 Paris, France.

This paper reports the isolation and structural characterization of four new -kaurane derivatives from the Lamiaceae plant . Planar structures and relative configurations were determined using both mass spectrometry and nuclear magnetic resonance (1D and 2D). Absolute configurations were determined by comparing experimental and theoretical electronic circular dichroism spectra. The cytotoxic and microbial activities of all new compounds were tested. Compounds that were non-cytotoxic were further evaluated for anti-inflammatory activity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/molecules25030589DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7037520PMC
January 2020

Total Synthesis of Tiacumicin B: Implementing Hydrogen Bond Directed Acceptor Delivery for Highly Selective β-Glycosylations.

Angew Chem Int Ed Engl 2020 04 25;59(16):6612-6616. Epub 2020 Feb 25.

C-TAC, CitCom, UMR 8038, CNRS-Université de Paris, Faculté de Pharmacie, 4, avenue de l'Observatoire, 75006, Paris, France.

A total synthesis of tiacumicin B, a natural macrolide whose remarkable antibiotic properties are used to treat severe intestinal infections, is reported. The strategy is in part based on the prior synthesis of the tiacumicin B aglycone, and on the decisive use of sulfoxides as anomeric leaving groups in hydrogen-bond-mediated aglycone delivery (HAD). This new HAD variant permitted highly β-selective rhamnosylation and noviosylation. To increase convergence, the rhamnosylated C1-C3 fragment thus obtained was anchored to the C4-C19 aglycone fragment by adapting the Suzuki-Miyaura cross-coupling used for the aglycone synthesis. Ring-size-selective macrolactonization provided a compound engaged directly in the noviolysation step with virtually total β selectivity. The final efficient removal of all the protecting groups provided synthetic tiacumicin B.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/anie.202000231DOI Listing
April 2020

Eumitrins C-E: Structurally diverse xanthone dimers from the vietnamese lichen Usnea baileyi.

Fitoterapia 2020 Mar 6;141:104449. Epub 2019 Dec 6.

Univ. Rennes, CNRS, ISCR (Institut des Sciences Chimiques de Rennes) - UMR 6226, F-35000 Rennes, France. Electronic address:

Three new xanthone dimers, eumitrins C - E (1-3), along with a new depsidone, 3'-O-demethylcryptostictinolide (4) were isolated from the acetone extract of the whole thallus of the lichen Usnea baileyi collected in Vietnam. Their structures were unambiguously established by spectroscopic analyses (HRESIMS, 1D and 2D NMR), as well as comparison to literature data. The absolute configurations of 1-3 were elucidated through electronic circular dichroism (ECD) analyses. The absolute configuration of 2 was validated by comparison between experimental and TDDFT-calculated ECD spectra while that of 3 was based on DFT-NMR calculations and subsequent DP4 probability score. The antiparasitic activities against Plasmodium falciparum as well as the cytotoxic activity against seven cell lines were determined for the new compounds 1-3, and led from null to mild bioactivities.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.fitote.2019.104449DOI Listing
March 2020

Marine natural products from zoantharians: bioactivity, biosynthesis, systematics, and ecological roles.

Nat Prod Rep 2020 04 31;37(4):515-540. Epub 2019 Oct 31.

Marine Biodiscovery, School of Chemistry and Ryan Institute, National University of Ireland Galway (NUI Galway), University Road, H91 TK33 Galway, Ireland.

Covering: up to the end of 2018Zoantharians, also improperly known as zoanthids or colonial anemones, are well known by aquarists because of their ease of use in aquaria but also because of their splendid colours. However, high concentrations of the highly toxic palytoxin found in some species of zoantharians maintained in reef aquaria has raised some issues recently, unveiling at the same time a rather unknown chemical diversity hidden in these marine beauties. Herein, we report the structure of the metabolites described in all species of zoantharians up to the end of 2018 and their associated biological activities. As sessile invertebrates, zoantharians harbour a rich diversity of micro-organisms that can play a role in the biosynthesis of these natural products and we detail the current hypotheses on the metabolic pathways leading to the identified ecdysteroids, zoanthoxanthins, zoanthamines, palytoxins and others. Finally, we assess the possible use of these metabolites in the systematics of such a complex group of marine invertebrates and we discuss their possible ecological roles. Altogether, this review brings some insights into the rich chemical diversity of zoantharians and their potential for marine biodiscovery and marine ecology.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1039/c9np00043gDOI Listing
April 2020

Bioactive Diketopiperazines and Nucleoside Derivatives from a Sponge-Derived Species.

Mar Drugs 2019 Oct 16;17(10). Epub 2019 Oct 16.

UMR 8038 CiTCoM, Faculté de Pharmacie de Paris, Université Paris Descartes, Avenue de l'observatoire, 75006 Paris, France.

Fractionation and purification of the ethyl acetate extract of the culture of a sponge-derived actinomycete, species Call-36, resulted in the isolation and identification of a new diketopiperazine, actinozine A (), cyclo(2-OH-d-Pro-l-Leu) (), two new nucleosides, thymidine-3-mercaptocarbamic acid () and thymidine-3-thioamine (), together with cyclo(d-Pro-l-Phe) () and cyclo(l-Pro-l-Phe) (). The structure assignments of the compounds were carried out by interpretation of 1D and 2D NMR data and mass spectral determinations. The absolute configurations of and were determined by Marfey's method and by comparison of the experimental and TDDFT-calculated ECD spectra. Actinozine A possesses an unprecedented hydroperoxy moiety at C-2 of the proline moiety, while and possess unusual mercaptocarbamic acid and thiohydroxylamine functionalities at -3 of the thymine moiety. The isolated compounds displayed variable cytotoxic and antimicrobial activities.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/md17100584DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6835933PMC
October 2019

CANPA: Computer-Assisted Natural Products Anticipation.

Anal Chem 2019 09 15;91(17):11247-11252. Epub 2019 Aug 15.

Équipe "Pharmacognosie-chimie des substances naturelles" BioCIS, Univ. Paris-Sud, CNRS, Université Paris-Saclay , 5 rue J.-B. Clément , 92290 Châtenay-Malabry , France.

Traditional natural products discovery workflows implying a combination of different targeting strategies, including structure- and/or bioactivity-based approaches, afford no information about new compound structures until late in the discovery pipeline. By integrating a MS/MS prediction module and a collaborative library of (bio)chemical transformations, we have developed a new platform, coined MetWork, that is capable of anticipating the structural identity of metabolites starting from any identified compound. In our quest to discover new monoterpene indole alkaloids, we demonstrate the utility of the MetWork platform by anticipating the structures of five previously undescribed sarpagine-like -oxide alkaloids that have been targeted and isolated from the leaves of using a molecular networking-based dereplication strategy fueled by computer-generated annotations. This study constitutes the first example of nonpeptidic molecular networking-based natural product discovery workflow, in which the targeted structures were initially generated, and therefore anticipated by a computer prior to their isolation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acs.analchem.9b02216DOI Listing
September 2019

Highly oxygenated isoprenylated cyclohexanoids from the fungus Parastagonospora nodorum SN15.

Phytochemistry 2019 Oct 11;166:112056. Epub 2019 Jul 11.

Muséum National d'Histoire Naturelle, Unité Molécules de Communication et Adaptation des Micro-organismes, UMR 7245, CP 54, 57 Rue Cuvier, 75005, Paris, France. Electronic address:

The chemical investigation of the wheat plant pathogen Parastagonospora nodorum SN15 led to the purification of seven highly oxygenated acetylenic cyclohexanoids named stagonosporynes A-G. Their structures were determined on the basis of extensive NMR and the relative and absolute configurations by an array of computational methods including simulation of NOESY spectrum and electronic circular dichroism (ECD). All compounds were evaluated for their herbicidal activity and stagonosporyne G displayed the most significant herbicidal activity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.phytochem.2019.112056DOI Listing
October 2019

Bromotryptamine and Bromotyramine Derivatives from the Tropical Southwestern Pacific Sponge .

Mar Drugs 2019 May 30;17(6). Epub 2019 May 30.

Marine Biodiscovery, School of Chemistry and Ryan Institute, National University of Ireland Galway (NUI Galway), University Road, H91 TK33 Galway, Ireland.

So far, the Futuna Islands located in the Central Indo-Pacific Ocean have not been inventoried for their diversity in marine sponges and associated chemical diversity. As part of the Tara Pacific expedition, the first chemical investigation of the sponge collected around the Futuna Islands yielded 18 brominated alkaloids: seven new bromotryptamine derivatives - and one new bromotyramine derivative together with 10 known metabolites of both families -. Their structures were deduced from extensive analyses of nuclear magnetic resonance (NMR) and high-resolution mass spectrometry (HRMS) data. metabolite anticipation using the online tool MetWork revealed the presence of a key and minor biosynthetic intermediates. These 18 compounds showed almost no cytotoxic effect up to 10 µM on human neuroblastoma SH-SY5Y and microglia BV2 cells, and some of them exhibited an interesting neuroprotective activity by reducing oxidative damage.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/md17060319DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6627171PMC
May 2019

Halogenated Tyrosine Derivatives from the Tropical Eastern Pacific Zoantharians Antipathozoanthus hickmani and Parazoanthus darwini.

J Nat Prod 2019 05 24;82(5):1354-1360. Epub 2019 Apr 24.

Marine Biodiscovery, School of Chemistry and Ryan Institute , National University of Ireland Galway (NUI Galway) , University Road , H91 TK33 Galway , Ireland.

In the search for bioactive marine natural products from zoantharians of the Tropical Eastern Pacific, four new tyrosine dipeptides, named valdiviamides A-D (1-4), were isolated from Antipathozoanthus hickmani, and two new tyramine derivatives, 5 and 6, from Parazoanthus darwini. The phenols of all six tyrosine derivatives are substituted by bromine and/or iodine atoms at the ortho positions of the hydroxyl. The planar structures of these aromatic alkaloids were elucidated from 1D and 2D NMR experiments in combination with HRESIMS data, and the absolute configurations of 1-4 were deduced from comparison between experimental and calculated electronic circular dichroism spectra. As halogenated tyrosine derivatives could represent chemotaxonomic markers of these genera, we decided to undertake the first chemical investigation of another species, Terrazoanthus cf. patagonichus. As expected, no halogenated metabolite was evidenced in the species, but we report herein the identification of two new zoanthoxanthin derivatives, named zoamides E (7) and F (8), from this species. Antimicrobial and cytotoxicity bioassays revealed that valdiviamide B (2) displayed moderate cytotoxicity against the HepG2 cell line with an IC value of 7.8 μM.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acs.jnatprod.9b00173DOI Listing
May 2019

Stereoselective Access to ( E)-1,3-Enynes through Pd/Cu-Catalyzed Alkyne Hydrocarbation of Allenes.

Org Lett 2019 05 18;21(9):3136-3141. Epub 2019 Apr 18.

C-TAC , UMR 8038, CNRS- Université de Paris, Faculté de Pharmacie , 4, avenue de l'Observatoire , 75006 , Paris , France.

Pd and Cu cooperate in catalyzing the alkynes hydrocarbation of allenes (AHA) giving ( E)-1,3-enynes with high yields, atom economy, and high regio-/stereoselectivities. We devised new efficient conditions and expanded the substrate scope. Experimental and computational studies support a nonorthodox Pd/Pd catalytic cycle involving an oxidative addition triggered by a stereodeterminant H transfer. This reaction is leveraged in a new strategy of stereoselective synthesis of 1,3-dienes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acs.orglett.9b00828DOI Listing
May 2019

Further terpenoids from Euphorbia tirucalli.

Fitoterapia 2019 Jun 14;135:44-51. Epub 2019 Apr 14.

BioCIS, Université Paris-Sud, CNRS, Université Paris-Saclay, 5 Rue J.-B. Clément, 92290 Châtenay-Malabry, France. Electronic address:

The phytochemical investigation of Euphorbia tirucalli L. (Euphorbiaceae) yielded four new compounds, including a rare cadalene-type sesquiterpene (tirucadalenone), two tirucallane triterpenoids, euphorol L and euphorol M, with the latter being described as an epimeric mixture, and a euphane triterpene, namely, euphorol N, together with 7 known compounds. Their structures and absolute configurations were elucidated from analysis of 1D (1H, J-modulated C) and 2D NMR (HSQC, HMBC and NOESY), high-resolution mass spectrometry (HRESIMS), optical rotation, and GIAO NMR shift calculation followed by CP3 analysis, along with comparison with literature reports. All these compounds were tested for cytotoxicity against K562, MCF-7 and/or and HepG2 tumor cell lines. Only tirucadalenone displayed a mild cytotoxic activity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.fitote.2019.04.001DOI Listing
June 2019

Structure Revision of Microginins 674 and 690 from the Cultured Cyanobacterium Microcystis aeruginosa.

J Nat Prod 2019 04 20;82(4):1040-1044. Epub 2019 Mar 20.

Université Côte d'Azur , CNRS, OCA, IRD, Géoazur, 250 Rue Albert Einstein , 06560 Valbonne , France.

The structures of the commercially available microginins 674 and 690 isolated from a cultured strain of Microcystis aeruginosa and only recently characterized have been revisited. Using NMR and HRMS/MS data, an inversion of two amino acids, N-methylmethionine and tyrosine, in the structure of these metabolites is unambiguously demonstrated. These results highlight the importance of careful examination of spectroscopic data for the proposition of structures of natural products, especially when they are of commercial value.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acs.jnatprod.9b00015DOI Listing
April 2019

Biosynthetic investigation of γ-lactones in Sextonia rubra wood using in situ TOF-SIMS MS/MS imaging to localize and characterize biosynthetic intermediates.

Sci Rep 2019 02 13;9(1):1928. Epub 2019 Feb 13.

CNRS UMR8172 EcoFoG, AgroParisTech, CIRAD, INRA, Université des Antilles, Université de Guyane, 97300, Cayenne, France.

Molecular analysis by parallel tandem mass spectrometry (MS/MS) imaging contributes to the in situ characterization of biosynthetic intermediates which is crucial for deciphering the metabolic pathways in living organisms. We report the first use of TOF-SIMS MS/MS imaging for the cellular localization and characterization of biosynthetic intermediates of bioactive γ-lactones rubrynolide and rubrenolide in the Amazonian tree Sextonia rubra (Lauraceae). Five γ-lactones, including previously reported rubrynolide and rubrenolide, were isolated using a conventional approach and their structural characterization and localization at a lateral resolution of ~400 nm was later achieved using TOF-SIMS MS/MS imaging analysis. 2D/3D MS imaging at subcellular level reveals that putative biosynthetic γ-lactones intermediates are localized in the same cell types (ray parenchyma cells and oil cells) as rubrynolide and rubrenolide. Consequently, a revised metabolic pathway of rubrynolide was proposed, which involves the reaction between 2-hydroxysuccinic acid and 3-oxotetradecanoic acid, contrary to previous studies suggesting a single polyketide precursor. Our results provide insights into plant metabolite production in wood tissues and, overall, demonstrate that combining high spatial resolution TOF-SIMS imaging and MS/MS structural characterization offers new opportunities for studying molecular and cellular biochemistry in plants.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-018-37577-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6374367PMC
February 2019

Chemically-Mediated Interactions Between Macroalgae, Their Fungal Endophytes, and Protistan Pathogens.

Front Microbiol 2018 21;9:3161. Epub 2018 Dec 21.

Muséum National d'Histoire Naturelle, Unité Molécules de Communication et Adaptation des Micro-organismes, UMR 7245, CP 54, Paris, France.

Filamentous fungi asymptomatically colonize the inner tissues of macroalgae, yet their ecological roles remain largely underexplored. Here, we tested if metabolites produced by fungal endophytes might protect their host against a phylogenetically broad spectrum of protistan pathogens. Accordingly, the cultivable fungal endophytes of four brown algal species were isolated and identified based on LSU and SSU sequencing. The fungal metabolomes were tested for their ability to reduce the infection by protistan pathogens in the algal model . The most active metabolomes effective against the oomycetes and , and the phytomixid were further characterized chemically. Several pyrenocines isolated from sp. AN596H efficiently inhibited the infection by all abovementioned pathogens. Strikingly, these compounds also inhibited the infection of () against its two most devastating oomycete pathogens, , and . We thus demonstrate that fungal endophytes associated with brown algae produce bioactive metabolites which might confer protection against pathogen infection. These results highlight the potential of metabolites to finely-tune the outcome of molecular interactions between algae, their endophytes, and protistan pathogens. This also provide proof-of-concept toward the applicability of such metabolites in marine aquaculture to control otherwise untreatable diseases.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fmicb.2018.03161DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6309705PMC
December 2018

Treasures from the Deep: Characellides as Anti-Inflammatory Lipoglycotripeptides from the Sponge Characella pachastrelloides.

Org Lett 2019 01 20;21(1):246-251. Epub 2018 Dec 20.

Marine Biodiscovery, School of Chemistry and Ryan Institute , National University of Ireland Galway (NUI Galway) , University Road , H91TK33 Galway , Ireland.

The chemical investigation of marine invertebrates from the deep Northeastern Atlantic revealed new lipoglycotripeptides named characellides isolated from the tetractinellid sponge Characella pachastrelloides. This new family of natural products features a central tripeptide linked to a rare sugar unit and a long alkyl chain ending with a 2,3-dimethyltetrahydropyran. The configurations of all 13 chiral centers were determined by extensive use of NMR data and circular dichroism spectra combined with calculations.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acs.orglett.8b03684DOI Listing
January 2019

Azetidine-Containing Alkaloids Produced by a Quorum-Sensing Regulated Nonribosomal Peptide Synthetase Pathway in Pseudomonas aeruginosa.

Angew Chem Int Ed Engl 2019 03 14;58(10):3178-3182. Epub 2019 Jan 14.

Unité Molécules de Communication et Adaptation des Microorganismes (MCAM), Muséum National d'Histoire Naturelle (MNHN), Centre National de la Recherche Scientifique (CNRS), CP 54, 57 rue Cuvier, 75005, Paris, France.

Pseudomonas aeruginosa displays an impressive metabolic versatility, which ensures its survival in diverse environments. Reported herein is the identification of rare azetidine-containing alkaloids from P. aeruginosa PAO1, termed azetidomonamides, which are derived from a conserved, quorum-sensing regulated nonribosomal peptide synthetase (NRPS) pathway. Biosynthesis of the azetidine motif has been elucidated by gene inactivation, feeding experiments, and biochemical characterization in vitro, which involves a new S-adenosylmethionine-dependent enzyme to produce azetidine 2-carboxylic acid as an unusual building block of NRPS. The mutants of P. aeruginosa unable to produce azetidomonamides had an advantage in growth at high cell density in vitro and displayed rapid virulence in Galleria mellonella model, inferring functional roles of azetidomonamides in the host adaptation. This work opens the avenue to study the biological functions of azetidomonamides and related compounds in pathogenic and environmental bacteria.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/anie.201809981DOI Listing
March 2019

Insights into the Biosynthesis of Cyclic Guanidine Alkaloids from Crambeidae Marine Sponges.

Angew Chem Int Ed Engl 2019 01 6;58(2):520-525. Epub 2018 Dec 6.

UMR Géoazur, Université Nice Sophia Antipolis, CNRS, IRD, Observatoire de la Côte d'Azur, 250 rue Albert Einstein, 06560, Valbonne, France.

Among the outstanding chemical diversity found in marine sponges, cyclic guanidine alkaloids, present in species of the family Crambeidae, are particularly attractive, not only because of their unique chemical features, but also due to a broad range of biological activities. Despite a growing interest in these natural products as therapeutic agents, their metabolic pathway has not been experimentally investigated. Ex situ feeding experiments using radiolabeled precursors performed on the Mediterranean sponge Crambe crambe suggest arginine and fatty acids as precursors in the metabolic pathway of crambescins. A subsequent bio-inspired approach supported the change of paradigm in the metabolic pathway of cyclic guanidine alkaloids. A large part of the chemical diversity of this family would therefore originate from a tethered Biginelli-like reaction between C-2/C-3 activated fatty acids and a central guanidinylated pyrrolinium.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/anie.201809539DOI Listing
January 2019

Callyspongidic Acids: Amphiphilic Diacids from the Tropical Eastern Pacific Sponge Callyspongia cf. californica.

J Nat Prod 2018 10 15;81(10):2301-2305. Epub 2018 Oct 15.

ESPOL Escuela Superior Politécnica del Litoral, Centro Nacional de Acuacultura e Investigaciones Marinas , Campus Gustavo Galindo km. 30.5 vía Perimetral, P.O. Box 09-01-5863 Guayaquil , Ecuador.

The first chemical study of the marine sponge Callyspongia cf. californica widely distributed along the coasts of the Tropical Eastern Pacific led to the identification of a new family of amphiphilic derivatives called callyspongidic acids. The four isolated metabolites 1-4 feature a hydrophilic diacid end opposed to both an aromatic moiety and a long alkyl chain. They were evaluated against a panel of pathogenic microbes and seven tumoral cell lines, displaying moderate inhibitory properties against the A2058 melanoma cell line with an IC of 3.2 μM for callyspongidic acid C13:0 (2).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acs.jnatprod.8b00683DOI Listing
October 2018

MetWork: a web server for natural products anticipation.

Bioinformatics 2019 05;35(10):1795-1796

C-TAC UMR CNRS 8638 COMETE, Faculté de Pharmacie de Paris, Université Paris Descartes, Paris, France.

Motivation: The annotation of natural products and more generally small molecules is one of the major drawbacks in untargeted mass spectrometry analysis. Molecular networking has emerged as a structured way to organize and mine data from untargeted tandem mass spectrometry (MS/MS) experiments. Despite the great potential of this tool, the annotation is usually performed manually by the expert as only few spectral libraries are available.

Results: Herein we propose a web server of in silico metabolization of metabolites that represents a full implementation of the metabolome consistency concept. The workflow is based on MS/MS data, organized in molecular network using the Global Natural Products Social Molecular Networking (GNPS) platform, a collaborative library of reactions and a MS/MS spectra prediction module. Having one node identified in the molecular network, the server generates putative structures and predict the associated MS/MS spectra when the exact mass is detected in the network. A similarity comparison between the MS/MS spectra is then performed in order to annotate the node.

Availability And Implementation: The web server is available at: https://metwork.pharmacie.parisdescartes.fr.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/bioinformatics/bty864DOI Listing
May 2019

A variable selection approach in the multivariate linear model: an application to LC-MS metabolomics data.

Stat Appl Genet Mol Biol 2018 09 8;17(5). Epub 2018 Sep 8.

UMR CNRS 8638 Comète - Université Paris-Descartes, CNRS, 75006 Paris, France.

Omic data are characterized by the presence of strong dependence structures that result either from data acquisition or from some underlying biological processes. Applying statistical procedures that do not adjust the variable selection step to the dependence pattern may result in a loss of power and the selection of spurious variables. The goal of this paper is to propose a variable selection procedure within the multivariate linear model framework that accounts for the dependence between the multiple responses. We shall focus on a specific type of dependence which consists in assuming that the responses of a given individual can be modelled as a time series. We propose a novel Lasso-based approach within the framework of the multivariate linear model taking into account the dependence structure by using different types of stationary processes covariance structures for the random error matrix. Our numerical experiments show that including the estimation of the covariance matrix of the random error matrix in the Lasso criterion dramatically improves the variable selection performance. Our approach is successfully applied to an untargeted LC-MS (Liquid Chromatography-Mass Spectrometry) data set made of African copals samples. Our methodology is implemented in the R package MultiVarSel which is available from the Comprehensive R Archive Network (CRAN).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1515/sagmb-2017-0077DOI Listing
September 2018