Publications by authors named "Patrick Chaimbault"

26 Publications

  • Page 1 of 1

Elicitation of Antimicrobial Active Compounds by -Fungus Co-Cultures.

Microorganisms 2021 Jan 15;9(1). Epub 2021 Jan 15.

Université de Lorraine, INRAE, DynAMic, F-54000 Nancy, France.

The bacteria of the genus and Basidiomycete fungi harbor many biosynthetic gene clusters (BGCs) that are at the origin of many bioactive molecules with medical or industrial interests. Nevertheless, most BGCs do not express in standard lab growth conditions, preventing the full metabolic potential of these organisms from being exploited. Because it generates biotic cues encountered during natural growth conditions, co-culture is a means to elicit such cryptic compounds. In this study, we explored 72 different -fungus interaction zones (SFIZs) generated during the co-culture of eight and nine fungi. Two SFIZs were selected because they showed an elicitation of anti-bacterial activity compared to mono-cultures. The study of these SFIZs showed that co-culture had a strong impact on the metabolic expression of each partner and enabled the expression of specific compounds. These results show that mimicking the biotic interactions present in this ecological niche is a promising avenue of research to explore the metabolic capacities of and fungi.
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http://dx.doi.org/10.3390/microorganisms9010178DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7830452PMC
January 2021

Metabolomics approach based on LC-HRMS for the fast screening of iron(II)-chelating peptides in protein hydrolysates.

Anal Bioanal Chem 2021 Jan 2;413(2):315-329. Epub 2021 Jan 2.

Université de Lorraine, LCP-A2MC, 57000, Metz, France.

Production of iron-chelating peptides from protein hydrolysates requires robust and adequate screening methods to optimize their purification and subsequently valorize their potential antioxidant properties. An original methodology was developed for direct and sensitive screening of iron(II)-chelating peptides based on ion-pair reverse phase liquid chromatography (IP-RPLC) coupled to high-resolution mass spectrometry (HRMS). Peptide mixture was first added to iron(II) solution to form iron(II)-peptide complexes. Then IP-RPLC-HRMS analysis was conducted on this iron-peptide mixture and on the iron-free peptide solution for comparative mass spectra analysis. This protocol, initially applied to a range of low molecular weight standard peptides, allowed detection of [(Peptide-H)+Fe] complex ion for iron(II)-chelating peptides (GGH, EAH, DAH, βAH, DMH, DTH, DSH). GGH was added in complex peptide mixtures and targeted analysis of [(GGH-H)+Fe] complex showed a limit of detection (LOD) below 0.77 mg L of GGH. This protocol was finally tested in combination with metabolomics software and additional digital processing for non-targeted search for iron(II)-chelating peptides. Applicability of this new screening methodology has been validated by detection of GGH as iron(II)-chelating peptide when added at 0.77 mg L in casein hydrolysate. Graphical abstract.
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http://dx.doi.org/10.1007/s00216-020-03037-1DOI Listing
January 2021

New approach in the characterization of bioactive compounds isolated from Calycotome spinosa (L.) Link leaves by the use of negative electrospray ionization LITMS, LC-ESI-MS/MS, as well as NMR analysis.

Bioorg Chem 2020 03 23;96:103535. Epub 2019 Dec 23.

Laboratoire de Mycologie, de Biotechnologie et de l'Activité Microbienne (LaMyBAM), Département de Biologie Appliquée, Université des Frères Mentouri, Constantine1, BP, 325 Route de Aïn El Bey, Constantine 25017, Algeria.

Two novel compounds were isolated for the first time from Calycotome spinosa (L.) Link, an alkaloid 5-Hydroxy-1H-indole (4) and a cyclitol D-pinitol (5), together with the three well-known flavonoids; Chrysin-7-O-(β-D-glucopyranoside) (1), Chrysin-7-O-β-D-(6″-acetyl)glycopyranoside (2) and Apigenin-7-O-β-D-glycopyranoside (3). The chemical structures of the isolated compounds were elucidated by spectroscopic data and mass spectrometric analyses; including a fresh approach 1D-NMR, 2D-NMR with LC-ESI-MS/MS. In this study, the new compound (4) that has been obtained from the leaves MeOH extract presented the best radical scavenging activity (DPPH) (IC < 10 µg/mL) compared to the standard butylated hydroxytoluene (BHT, IC = 34.73 ± 0.23 μg/mL) and showed the highest total antioxidant capacity (TAC = 985.54 ± 0.13 mg AAE/g extract) in contrast to ascorbic acid (TAC = 905.95 ± 0.07 mg AAE/g extract). Furthermore, the strongest reducing power (EC = 344.82 ± 0.02 µg/mL), as well as the remarkable scavenging potential by ABTS assay (IC = 7.8 ± 0.43 µg/mL), were exhibited by the same composite (4). Followed by the methanol crude extract and the compound (3) that also showed a potent antioxidant (DPPH; IC = 41.04 ± 0.15 and 47.36 ± 0.21 µg/mL, TAC; 671.02 ± 0.21 and 608.67 ± 0.34 mg AAE/g extract, FRAP; EC = 763.73 ± 0.32 and 814.61 ± 0.31 µg/mL, ABTS; IC = 19.18 ± 0.06 and 63.72 ± 0.64 µg/mL, respectively), but less than the previous samples. On the opposite side, compound (5) had the lowest activity, in which its values were less interesting to determine. Moreover, compound (4) has equally exerted an attractive antibacterial activity against Staphylococcus aureus (ATTC-25923), Pseudomonas aeruginosa (ATTC- 27853) and Salmonella abony (NCTC 6017), as measured by the disc diffusion assay, with inhibition zones of 16 ± 0.5, 9.83 ± 0.29 and 8 ± 0.28 mm, in that order. To the best of our knowledge, 5-Hydroxy-1H-indole was isolated from plants for the second time in our current work. Thus, the obtained results from this investigation propose that the leaves of C. spinosa are a rich natural source for value molecules as potential antioxidants and antimicrobial agents for best human health.
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http://dx.doi.org/10.1016/j.bioorg.2019.103535DOI Listing
March 2020

Personalized nutrition in ageing society: redox control of major-age related diseases through the NutRedOx Network (COST Action CA16112).

Free Radic Res 2019 22;53(sup1):1163-1170. Epub 2019 Feb 22.

Laboratoire Bio-PeroxIL EA7270, University Bourgogne Franche-Comté, Dijon, France.

A healthy ageing process is important when it is considered that one-third of the population of Europe is already over 50 years old, although there are regional variations. This proportion is likely to increase in the future, and maintenance of vitality at an older age is not only an important measure of the quality of life but also key to participation and productivity. So, the binomial "nutrition and ageing" has different aspects and poses considerable challenges, providing a fertile ground for research and networks. The NutRedOx network will focus on the impact of redox-active compounds in food on healthy ageing, chemoprevention, and redox control in the context of major age-related diseases. The main aim of the NutRedOx network is to gather experts from Europe, and neighbouring countries, and from different disciplines that are involved in the study of biological redox active food components and are relevant to the ageing organism, its health, function, and vulnerability to disease. Together, these experts will form a major and sustainable EU-wide cluster in form of the NutRedOx Centre of Excellence able to address the topic from different perspectives, with the long-term aim to provide a scientific basis for improved nutritional and lifestyle habits, to train the next generation of multidisciplinary researchers in this field, to raise awareness of such habits among the wider population, and also to engage with industry to develop age-adequate foods and medicines.
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http://dx.doi.org/10.1080/10715762.2019.1572890DOI Listing
April 2020

Labeling nitrogen species with the stable isotope N for their measurement by separative methods coupled with mass spectrometry: A review.

Talanta 2019 Jan 5;191:491-503. Epub 2018 Sep 5.

Université de Lorraine, CITHEFOR, F-54000 Nancy, France. Electronic address:

Nitrogen and its numerous hydrogenated and oxygenated derivatives are of main importance in our environment and in living cells as well in both qualitative and quantitative aspects. Their monitoring is needed to evaluate all disturbances occurring in the nitrogen cycle and in pathophysiological events related to variations of nitric oxide (NO) bioavailability. Many analytical methods are devoted to the measurement of nitrogen species, especially those related to NO, in the environmental, biological and pharmacological fields, and they have already been compiled and discussed in numerous reviews. Nitrogen isotope (N) is stable and has a low level of natural abundance. Labeling nitrogen species with N associated with mass spectrometry (MS) gives rise to more mechanistic information and improved analytical performances compared to conventional methods. The present review is dedicated to the N labeling of related nitrogen species to monitor their interconversion and metabolism, the different chemical probes used for their derivatization and the corresponding separative methods coupled with MS for analyzing resulting adducts. The fragmentation mode of the different adducts and the resulting selectivity and sensitivity are discussed.
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http://dx.doi.org/10.1016/j.talanta.2018.09.011DOI Listing
January 2019

Higher-energy collision-induced dissociation for the quantification by liquid chromatography/tandem ion trap mass spectrometry of nitric oxide metabolites coming from S-nitroso-glutathione in an in vitro model of the intestinal barrier.

Rapid Commun Mass Spectrom 2019 Jan;33(1):1-11

LCP-A2MC, Université de Lorraine, F-57000, Metz, France.

Rationale: The potency of S-nitrosoglutathione (GSNO) as a nitric oxide (NO) donor to treat cardiovascular diseases (CVDs) has been highlighted in numerous studies. In order to study its bioavailability after oral administration, which represents the most convenient route for the chronic treatment of CVDs, it is essential to develop an analytical method permitting (i) the simultaneous measurement of GSNO metabolites, i.e. nitrite, S-nitrosothiols (RSNOs) and nitrate and (ii) to distinguish them from other sources (endogenous synthesis and diet).

Methods: Exogenous GSNO was labeled with N, and the GS NO metabolites after conversion into the nitrite ion were derivatized with 2,3-diaminonaphthalene. The resulting 2,3-naphthotriazole was quantified by liquid chromatography/tandem ion trap mass spectrometry (LC/ITMS/MS) in multiple reaction monitoring mode after Higher-energy Collision-induced Dissociation (HCD). Finally, the validated method was applied to an in vitro model of the intestinal barrier (monolayer of Caco-2 cells) to study GS NO intestinal permeability.

Results: A LC/ITMS/MS method based on an original transition (m/z 171 to 156) for sodium N-nitrite, GS NO and sodium N-nitrate measurements was validated, with recoveries of 100.8 ± 3.8, 98.0 ± 2.7 and 104.1 ± 3.3%, respectively. Intra- and inter-day variabilities were below 13.4 and 12.6%, and the limit of quantification reached 5 nM (signal over blank = 4). The permeability of labeled GS NO (10-100 μM) was evaluated by calculating its apparent permeability coefficient (P ).

Conclusions: A quantitative LC/ITMS/MS method using HCD was developed for the first time to selectively monitor GS NO metabolites. The assay allowed evaluation of GS NO intestinal permeability and situated this drug candidate within the middle permeability class according to FDA guidelines. In addition, the present method has opened the perspective of a more fundamental work aiming at studying the fragmentation mechanism leading to the ion at m/z 156 in HCD tandem mass spectrometry in the presence of acetonitrile.
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http://dx.doi.org/10.1002/rcm.8287DOI Listing
January 2019

Antibacterial activity and cytotoxicity of Pterocarpus erinaceus Poir extracts, fractions and isolated compounds.

J Ethnopharmacol 2018 Feb 6;212:200-207. Epub 2017 Nov 6.

CNRS, UMR 7565, SRSMC, F-54506 Vandoeuvre-lès-Nancy, France; Université de Lorraine, UMR 7565, SRSMC, F-54506 Vandoeuvre-lès-Nancy, France; ABC Platform®, Faculté de Pharmacie, F-54001 Nancy, France. Electronic address:

Ethnopharmacological Relevance: Pterocarpus erinaceus has been chosen based on ethnobotanical surveys carried out in the Tchamba district of the Republic of Togo.

Aim Of The Study: Investigation of the antibacterial as well as cytotoxic activities of whole extracts, fractions and compounds isolated from the leaves, trunk bark and roots of Pterocarpus erinaceus.

Materials And Methods: Bio-guided fractionation of the raw extracts of plant parts and subsequent isolation of compounds from active fractions using normal phase open column chromatography. The broth microdilution method was used to evaluate the antibacterial activity, based on the determination of Minimal Inhibitory Concentrations (MICs) against several bacterial species representative of the most commonly encountered infectious diseases worldwide. The cytotoxicity of the raw extract and the most active fractions on a human non-cancerous cell (namely MRC-5) was estimated with a MTT assay. The chemical structure of the compounds isolated was elucidated using a combination of advanced Nuclear Magnetic Resonance (NMR) and Mass Spectrometry (MS).

Results: All extracts and fractions tested have shown good activities against Gram-positive bacteria (including Methicillin-Resistant Staphylococcus aureus, MRSA) and against Pseudomonas aeruginosa with MIC values ranging from 32µg/mL to 256µg/mL. In contrast, extracts were not toxic to MRC-5 cells. Four compounds have been isolated: Compound 1 (friedeline); Compound 2 (2,3 dihydroxypropyloctacosanoate); Compound 3 (a mixture of β-sitosterol, stigmasterol and campesterol); Compound 4 (β-sitosteryl-β-D-glucopyranoside) and shown to be active against some of the bacteria tested. They were active with MIC equal to 4µg/mL against strains of S. aureus (including MRSA). To the best of our knowledge, all of them except friedeline have never been reported in this plant species.

Conclusion: P. erinaceus is confirmed as a plant harboring promising antibacterial activity with activities against serious human pathogens at very low concentrations. Some of the compounds isolated are also active at concentrations as low as 4µg/mL and therefore, may provide new leads for the development of antibacterial agents.
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http://dx.doi.org/10.1016/j.jep.2017.10.020DOI Listing
February 2018

Tubulin-binding anticancer polysulfides induce cell death via mitotic arrest and autophagic interference in colorectal cancer.

Cancer Lett 2017 12 21;410:139-157. Epub 2017 Sep 21.

College of Pharmacy, Seoul National University, Seoul, 08826, South Korea. Electronic address:

Polysulfanes show chemopreventive effects against gastrointestinal tumors. We identified diallyl tetrasulfide and its derivative, dibenzyl tetrasulfide (DBTTS), to be mitotic inhibitors and apoptosis inducers. Here, we translate their application in colorectal cancer (CRC). MALDI-TOF-MS analysis identified both compounds as reversible tubulin binders, validated by in cellulo α-tubulin degradation. BRAF(V600E)-mutated HT-29 cells were resistant to DBTTS, as evidenced by mitotic arrest for 48 h prior to apoptosis induction compared to KRAS(G12V)-mutated SW480/620 cells, which committed to death earlier. The prolonged mitotic block correlated with autophagy impairment and p62 protein accumulation in HT-29 but not in SW480/620 cells, whereas siRNA-mediated p62 inhibition sensitized HT-29 cells to death. In silico analysis with 484 colorectal cancer patients associated higher p62 expression and reduced autophagic flux with greater overall survival. Accordingly, we hypothesized that DBTTS targets CRC survival/death through autophagy interference in cell types with differential autophagic capacities. We confirmed the therapeutic potential of DBTTS by the inhibition of spheroid and colony formation capacities in CRC cells, as well as in HT-29 zebrafish xenografts in vivo.
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http://dx.doi.org/10.1016/j.canlet.2017.09.011DOI Listing
December 2017

Correlative Analysis of Fluorescent Phytoalexins by Mass Spectrometry Imaging and Fluorescence Microscopy in Grapevine Leaves.

Anal Chem 2017 07 13;89(13):7099-7106. Epub 2017 Jun 13.

Université de Lorraine. Laboratoire de Chimie et Physique-Approche Multi échelle des Milieux Complexes (LCP-A2MC), EA 4632, Institut Jean Barriol - Fédération de Recherche 2843; ICPM 1, Boulevard Arago , Metz Technopole Cedex 03, F-57078, France.

Plant response to their environment stresses is a complex mechanism involving secondary metabolites. Stilbene phytoalexins, namely resveratrol, pterostilbene, piceids and viniferins play a key role in grapevine (Vitis vinifera) leaf defense. Despite their well-established qualities, conventional analyses such as HPLC-DAD or LC-MS lose valuable information on metabolite localization during the extraction process. To overcome this issue, a correlative analysis combining mass spectroscopy imaging (MSI) and fluorescence imaging was developed to localize in situ stilbenes on the same stressed grapevine leaves. High-resolution images of the stilbene fluorescence provided by macroscopy were supplemented by specific distributions and structural information concerning resveratrol, pterostilbene, and piceids obtained by MSI. The two imaging techniques led to consistent and complementary data on the stilbene spatial distribution for the two stresses addressed: UV-C irradiation and infection by Plasmopara viticola. Results emphasize that grapevine leaves react differently depending on the stress. A rather uniform synthesis of stilbenes is induced after UV-C irradiation, whereas a more localized synthesis of stilbenes in stomata guard cells and cell walls is induced by P. viticola infection. Finally, this combined imaging approach could be extended to map phytoalexins of various plant tissues with resolution approaching the cellular level.
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http://dx.doi.org/10.1021/acs.analchem.7b01002DOI Listing
July 2017

Natural and Synthetic Coumarins with Effects on Inflammation.

Molecules 2016 Oct 2;21(10). Epub 2016 Oct 2.

SRSMC, UMR 7565, Groupe HeCRIN, ICPM, 1 boulevard Arago, 57070 Metz, France.

In this review, we will present the different aspects of coumarins and derivatives, from natural origins or synthetically prepared, and their action on inflammation. Coumarins and also furo- and pyranocoumarins are found in many different plants. These compounds are very often investigated for antioxidant properties. Other biological properties are also possible and anti-inflammation activity is one of these. As coumarins are also available quite easily via synthesis, natural ones can be prepared this way but derivatives with special substituents are also feasible. A review on the same topic appeared in 2004 and our contribution will take into account everything published since then.
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http://dx.doi.org/10.3390/molecules21101322DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6273422PMC
October 2016

Screening of indeno[1,2-b]indoloquinones by MALDI-MS: a new set of potential CDC25 phosphatase inhibitors brought to light.

J Enzyme Inhib Med Chem 2016 30;31(sup3):25-32. Epub 2016 Jun 30.

d Université de Lorraine, Laboratoire de Structure et Réactivité des Systèmes Moléculaires Complexes (SRSMC), UMR CNRS 7565, Institut Jean Barriol FR2843 , Metz cedex 3 , France , and.

Quinones and quinones-like compounds are potential candidates for the inhibition of CDC25 phosphatases. The combination of MALDI-MS analyses and biological studies was used to develop a rapid screening of a targeted library of indeno[1,2-b]indoloquinone derivatives. The screening protocol using MALDI-TOFMS and MALDI-FTICRMS highlighted four new promising candidates. Biological investigations showed that only compounds 5c-f inhibited CDC25A and -C phosphatases, with IC values around the micromolar range. The direct use of a screening method based on MALDI-MS technology allowed achieving fast scaffold identification of a new class of potent inhibitors of CDC25 phosphatases. These four molecules appeared as novel molecules of a new class of CDC25 inhibitors. Assessment of 5c-e in an MRC5 proliferation assay provided an early indicator of toxicity to mammalian cells. Compound 5d seems the most promising hit for developing new CDC25 inhibitors.
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http://dx.doi.org/10.1080/14756366.2016.1201480DOI Listing
February 2017

2-(Thienothiazolylimino)-1,3-thiazolidin-4-ones inhibit cell division cycle 25 A phosphatase.

Bioorg Med Chem 2016 07 2;24(13):2920-2928. Epub 2016 May 2.

Université de Lorraine, UMR CNRS 7565, Structure et Réactivité des Systèmes Moléculaires Complexes, Equipe 5 (MIC), Campus Bridoux, rue du Général Delestraint, 57070 Metz Cedex, France. Electronic address:

Cell division cycle dual phosphatases (CDC25) are essential enzymes that regulate cell progression in cell cycle. Three isoforms exist as CDC25A, B and C. Over-expression of each CDC25 enzyme is found in cancers of diverse origins. Thiazolidinone derivatives have been reported to display anti-proliferative activities, bactericidal activities and to reduce inflammation process. New 2-(thienothiazolylimino)-1,3-thiazolidin-4-ones were synthesized and evaluated as inhibitors of CDC25 phosphatase. Among the molecules tested, compound 6 inhibited CDC25A with an IC50 estimated at 6.2±1.0μM. The binding of thiazolidinone derivative 6 onto CDC25A protein was reversible. In cellulo, compound 6 treatment led to MCF7 and MDA-MB-231 cell growth arrest. To our knowledge, it is the first time that such 4-thiazolidinone derivatives are characterized as CDC25 potential inhibitor.
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http://dx.doi.org/10.1016/j.bmc.2016.04.063DOI Listing
July 2016

Turning Waste into Value: Nanosized Natural Plant Materials of Solanum incanum L. and Pterocarpus erinaceus Poir with Promising Antimicrobial Activities.

Pharmaceutics 2016 Apr 19;8(2). Epub 2016 Apr 19.

Division of Bioorganic Chemistry, School of Pharmacy, Saarland University, Saarbruecken D-66123, Germany.

Numerous plants are known to exhibit considerable biological activities in the fields of medicine and agriculture, yet access to their active ingredients is often complicated, cumbersome and expensive. As a consequence, many plants harbouring potential drugs or green phyto-protectants go largely unnoticed, especially in poorer countries which, at the same time, are in desperate need of antimicrobial agents. As in the case of plants such as the Jericho tomato, Solanum incanum, and the common African tree Pterocarpus erinaceus, nanosizing of original plant materials may provide an interesting alternative to extensive extraction and isolation procedures. Indeed, it is straightforward to obtain considerable amounts of such common, often weed-like plants, and to mill the dried material to more or less uniform particles of microscopic and nanoscopic size. These particles exhibit activity against Steinernema feltiae or Escherichia coli, which is comparable to the ones seen for processed extracts of the same, respective plants. As S. feltiae is used as a model nematode indicative of possible phyto-protective uses in the agricultural arena, these findings also showcase the potential of nanosizing of crude "waste" plant materials for specific practical applications, especially-but not exclusively-in developing countries lacking a more sophisticated industrial infrastructure.
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http://dx.doi.org/10.3390/pharmaceutics8020011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4932474PMC
April 2016

Effect of Potassium on the Mechanisms of Biomass Pyrolysis Studied using Complementary Analytical Techniques.

ChemSusChem 2016 04 15;9(8):863-72. Epub 2016 Mar 15.

Reactions and processes Engineering laboratory, CNRS, Université de Lorraine, ENSIC, 1 rue Grandville, B.P.20451 54000, Nancy Cedex, France.

Complementary analytical methods have been used to study the effect of potassium on the pyrolysis mechanisms of cellulose and lignocellulosic biomasses. Thermogravimetry, calorimetry, high-temperature (1) H NMR spectroscopy (in situ and real-time analysis of the fluid phase formed during pyrolysis), and water extraction of quenched char followed by size-exclusion chromatography coupled with mass spectrometry have been combined. Potassium impregnated in cellulose suppresses the formation of anhydrosugars, reduces the formation of mobile protons, and gives rise to a mainly exothermic signal. The evolution of mobile protons formed from K-impregnated cellulose has a very similar pattern to the evolution of the mass loss rate. This methodology has been also applied to analyze miscanthus, demineralized miscanthus, miscanthus re-impregnated with potassium after demineralization, raw oak, and Douglas fir. Hydrogen mobility and transfer are of high importance in the mechanisms of biomass pyrolysis.
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http://dx.doi.org/10.1002/cssc.201501560DOI Listing
April 2016

New Peptide-Conjugated Chlorin-Type Photosensitizer Targeting Neuropilin-1 for Anti-Vascular Targeted Photodynamic Therapy.

Int J Mol Sci 2015 Oct 12;16(10):24059-80. Epub 2015 Oct 12.

LCPM UMR 7375, CNRS, ENSIC, 1 rue Grandville, BP 20451-54001 Nancy Cedex, France.

Photodynamic therapy (PDT) is a cancer treatment modality that requires three components, namely light, dioxygen and a photosensitizing agent. After light excitation, the photosensitizer (PS) in its excited state transfers its energy to oxygen, which leads to photooxidation reactions. In order to improve the selectivity of the treatment, research has focused on the design of PS covalently attached to a tumor-targeting moiety. In this paper, we describe the synthesis and the physico-chemical and photophysical properties of six new peptide-conjugated photosensitizers designed for targeting the neuropilin-1 (NRP-1) receptor. We chose a TPC (5-(4-carboxyphenyl)-10,15, 20-triphenyl chlorine as photosensitizer, coupled via three different spacers (aminohexanoic acid, 1-amino-3,6-dioxaoctanoic acid, and 1-amino-9-aza-3,6,12,15-tetraoxa-10-on-heptadecanoic acid) to two different peptides (DKPPR and TKPRR). The affinity towards the NRP-1 receptor of the conjugated chlorins was evaluated along with in vitro and in vivo stability levels. The tissue concentration of the TPC-conjugates in animal model shows good distribution, especially for the DKPPR conjugates. The novel peptide-PS conjugates proposed in this study were proven to have potential to be further developed as future NRP-1 targeting photodynamic therapy agent.
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http://dx.doi.org/10.3390/ijms161024059DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4632738PMC
October 2015

MALDI mass spectrometry imaging for the simultaneous location of resveratrol, pterostilbene and viniferins on grapevine leaves.

Molecules 2014 Jul 21;19(7):10587-600. Epub 2014 Jul 21.

Laboratoire de Chimie et Physique-Approche Multi échelle des Milieux Complexes (LCP-A2MC), Institut Jean Barriol (FR 2843), Université de Lorraine, ICPM 1 Boulevard Arago, F-57078 Metz, France.

To investigate the in-situ response to a stress, grapevine leaves have been subjected to mass spectrometry imaging (MSI) experiments. The Matrix Assisted Laser Desorption/Ionisation (MALDI) approach using different matrices has been evaluated. Among all the tested matrices, the 2,5-dihydroxybenzoic acid (DHB) was found to be the most efficient matrix allowing a broader range of detected stilbene phytoalexins. Resveratrol, but also more toxic compounds against fungi such as pterostilbene and viniferins, were identified and mapped. Their spatial distributions on grapevine leaves irradiated by UV show their specific colocation around the veins. Moreover, MALDI MSI reveals that resveratrol (and piceids) and viniferins are not specifically located on the same area when leaves are infected by Plasmopara viticola. Results obtained by MALDI mass spectrometry imaging demonstrate that this technique would be essential to improve the level of knowledge concerning the role of the stilbene phytoalexins involved in a stress event.
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http://dx.doi.org/10.3390/molecules190710587DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6271053PMC
July 2014

Evaluation of ∆2-pioglitazone, an analogue of pioglitazone, on colon cancer cell survival: Evidence of drug treatment association with autophagy and activation of the Nrf2/Keap1 pathway.

Int J Oncol 2014 Jul 29;45(1):426-38. Epub 2014 Apr 29.

University of Lorraine, CNRS Unit 7565 - SRSMC Campus Bridoux, F-57070 Metz, France.

Thiazolidinediones have been shown to exhibit anti-proliferative effects against cancer cells derived from diverse tissue origins both in vivo and in vitro. We studied the anti-proliferative impact of 5-{4-(2-(5-ethyl-pyridin-2-yl)-ethoxy)-benzylidene}-thiazolidine-2,4-dione (∆2-pioglitazone), an analogue of pioglitazone, which binds to the nuclear peroxisome proliferator activated receptor-γ without activating it, on human adenocarcinoma-derived HT29 and HCT116 cells. In HTC116 cells, exposure to ∆2-pioglitazone reduced cell growth, but HT29 cells reached the plateau phase of growth after three days. ∆2-pioglitazone treatment did not trigger cells to enter apoptosis but enhanced the autophagy process. The effect of ∆2-pioglitazone treatment was related to the increase of oxygen and nitric oxide-derived species production and decreased glutathione content. Moreover, pre-treatment with an antioxidant before addition of ∆2-pioglitazone limited cell growth inhibition, reduced the production of reactive species and attenuated autophagy within the cells. The impact of the drug was associated with activation of the Nrf2/Keap1 pathway as demonstrated by the increased protein content of several antioxidant enzymes, notably heme-oxygenase-1.
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http://dx.doi.org/10.3892/ijo.2014.2408DOI Listing
July 2014

A novel coumarin-quinone derivative SV37 inhibits CDC25 phosphatases, impairs proliferation, and induces cell death.

Mol Carcinog 2015 Mar 24;54(3):229-41. Epub 2013 Oct 24.

Laboratoire "Structure et Réactivité des Systèmes Moléculaires Complexes, UMR CNRS 7565, Université de Lorraine, Campus Bridoux, Rue du Général Delestraint, Metz, France; Laboratoire de Biologie Moléculaire et Cellulaire du Cancer, Fondation de Recherche Cancer et Sang, Hôpital Kirchberg, Luxembourg, Luxembourg.

Cell division cycle (CDC) 25 proteins are key phosphatases regulating cell cycle transition and proliferation by regulating CDK/cyclin complexes. Overexpression of these enzymes is frequently observed in cancer and is related to aggressiveness, high-grade tumors and poor prognosis. Thus, targeting CDC25 by compounds, able to inhibit their activity, appears a good therapeutic approach. Here, we describe the synthesis of a new inhibitor (SV37) whose structure is based on both coumarin and quinone moieties. An analytical in vitro approach shows that this compound efficiently inhibits all three purified human CDC25 isoforms (IC50 1-9 µM) in a mixed-type mode. Moreover, SV37 inhibits growth of breast cancer cell lines. In MDA-MB-231 cells, reactive oxygen species generation is followed by pCDK accumulation, a mark of CDC25 dysfunction. Eventually, SV37 treatment leads to activation of apoptosis and DNA cleavage, underlining the potential of this new type of coumarin-quinone structure.
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http://dx.doi.org/10.1002/mc.22094DOI Listing
March 2015

Metabolic study of grapevine leaves infected by downy mildew using negative ion electrospray--Fourier transform ion cyclotron resonance mass spectrometry.

Anal Chim Acta 2013 Sep 6;795:44-51. Epub 2013 Aug 6.

Université de Lorraine, Laboratoire de Chimie et Physique-Approche Multi échelle des Milieux Complexes (LCP-A2MC), EA 4632, Institut Jean Barriol, Fédération de Recherche 2843, ICPM 1, Metz Technopole Cedex 03, France.

Grapevine is of worldwide economic importance due to wine production. However, this culture is often affected by pathogens causing severe harvest losses. Understanding host-pathogen relationships may be a key to solve this problem. In this paper, we evaluate the direct flow injection by electrospray - Fourier transform ion cyclotron resonance mass spectrometry (MS) of leaf extracts as a rapid method for the study of grapevine response to downy mildew (Plasmopara viticola) attack. The comparison of MS profiles obtained from control and infected leaves of different levels of resistant grapevines highlights several classes of metabolites (mainly saccharides, acyl lipids, hydroxycinnamic acids derivatives and flavonoids) which are identified using high resolution MS and tandem MS (MS/MS). Statistical analyses of 19 markers show a clear segregation between inoculated and healthy samples. This study points out relative high levels of disaccharides, acyl lipids and glycerophosphoinositol in inoculated samples. Sulfoquinovosyl diacylglycerols also emerge as possible metabolites involved in plant defense.
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http://dx.doi.org/10.1016/j.aca.2013.07.068DOI Listing
September 2013

Pentacyclic triterpenes from Manilkara bidentata resin. Isolation, identification and biological properties.

Fitoterapia 2013 Jul 9;88:101-8. Epub 2013 May 9.

Institut de Chimie Organique et Analytique (ICOA), UMR-CNRS 7311, Université d'Orléans, Rue de Chartres, BP 6759 Orléans Cedex 2, France. Electronic address:

Three pentacyclic triterpenes were isolated for the first time from resinous plant Manilkara bidentata. Ultrasound-assisted extraction with ethanol was chosen after a comparison of various extraction methods. Analysis of the extract was performed by HPLC with evaporative light scattering detection and semi-preparative HPLC has enabled us to isolate two urs-12-enes (3β-O-acetyl-α-amyrin and 3β-O-trans cinnamyl-α-amyrin) and a lupane-type derivative (3β-O-trans cinnamyl lupeol). Structures were elucidated on the basis of HRESIMS, atmospheric pressure photoionization MS, and homo- and heteronuclear correlation NMR experiments. Antioxidant and anti-inflammatory activities were determined on Manilkara extract and isolated fractions. We have also investigated their action on collagen and fibronectin synthesis, two very important proteins of the extracellular matrix. Thus, Manilkara extract was able to decrease IL-1β and IL-8 pro-inflammatory cytokines. These activities exhibit the potential use of Manilkara extract as an anti-inflammatory and anti-aging ingredient for pharmaceutical and cosmetic industries.
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http://dx.doi.org/10.1016/j.fitote.2013.05.001DOI Listing
July 2013

Evaluation of combined matrix-assisted laser desorption/ionization time-of-flight and matrix-assisted laser desorption/ionization Fourier transform ion cyclotron resonance mass spectrometry experiments for peptide mass fingerprinting analysis.

Rapid Commun Mass Spectrom 2011 Jul;25(13):1881-92

Laboratoire de Spectrométrie de Masse et de Chimie Laser (LSMCL), Institut Jean Barriol - Fédération de Recherche 2843, Université Paul Verlaine - Metz, 1, Boulevard Arago, F-57078 Metz technopole Cedex 03, France.

Peptide Mass Fingerprinting (PMF) is still of significant interest in proteomics because it allows a large number of complex samples to be rapidly screened and characterized. The main part of post-translational modifications is generally preserved. In some specific cases, PMF suffers from ambiguous or unsuccessful identification. In order to improve its reliability, a combined approach using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOFMS) and matrix-assisted laser desorption/ionization Fourier transform ion cyclotron resonance mass spectrometry (MALDI-FTICRMS) was evaluated. The study was carried out on bovine serum albumin (BSA) digest. The influence of several important parameters (the matrix, the sample preparation method, the amount of the analyte) on the MOWSE score and the protein sequence coverage were evaluated to allow the identification of specific effects. A careful investigation of the sequence coverage obtained by each kind of experiment ensured the detection of specific peptides for each experimental condition. Results highlighted that DHB-FTICRMS and DHB- or CHCA-TOFMS are the most suited combinations of experimental conditions to achieve PMF analysis. The association (convolution) of the data obtained by each of these techniques ensured a significant increase in the MOWSE score and the protein sequence coverage.
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http://dx.doi.org/10.1002/rcm.5057DOI Listing
July 2011

Development of a LC-MS/MS method to monitor palmitoyl peptides content in anti-wrinkle cosmetics.

Anal Chim Acta 2009 May 20;641(1-2):95-100. Epub 2009 Mar 20.

Institut de Chimie Organique et Analytique, CNRS UMR 6005, Université d'Orléans, Rue de Chartres, BP 6759, 45067 Orléans Cedex 2, France.

Palmitoyl peptides are anti-aging agents widely used in cosmetics. This article describes the development of a LC-MS/MS analytical procedure that allows, after a liquid-liquid extraction procedure, their unambiguous detection in cosmetic formulation. MS/MS detection is shown to be specific regarding placebo formulations. Limits of quantification, linearity, accuracy and precision of the method were estimated. The results presented show that palmitoyl peptides can be thus reliably assayed. The palmitoylated pentapeptide palmitoyl-lysyl-threonyl-threonyl-lysyl-serine (pal-KTTKS) was assayed in anti-wrinkle creams using palmitoyl-glycyl-histidyl-lysine (pal-GHK) as internal standard. From the results obtained, the influence of the formulation on pal-KTTKS availability is evidenced.
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http://dx.doi.org/10.1016/j.aca.2009.03.015DOI Listing
May 2009

Mass spectrometry based methods for analysis of nucleosides as antiviral drugs and potential tumor biomarkers.

Nucleosides Nucleotides Nucleic Acids 2007 ;26(10-12):1523-7

Institut de Chimie Organique et Analytique, UMR CNRS 6005, Université d'Orléans, 45067 Orléans Cedex 2, France.

The intracellular analysis of the phosphorylated metabolites of some anti-HIV nucleosides by liquid chromatography or capillary electrophoresis coupled with tandem mass spectrometry (LC-MS/MS or CE-MS/MS) has been realized on human peripheral blood mononuclear cells (PBMC), with limit of quantitation (LOQ) that allow them to be quantitated intracellularly. We described also the analysis of modified urinary nucleosides as potential tumor biomarkers.
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http://dx.doi.org/10.1080/15257770701544336DOI Listing
March 2008

Analysis of native amino acids by liquid chromatography/electrospray ionization mass spectrometry: comparative study between two sources and interfaces.

J Mass Spectrom 2008 Feb;43(2):204-15

Institut de Chimie Organique et Analytique (ICOA), CNRS FR 2708, UMR 6005, Université d'Orléans, BP 6759, F-45067 Orléans Cedex 2, France.

The analytical performances of two triple-quadrupole instruments, which differ in their atmospheric-pressure sources, were evaluated for native amino acid analysis. The Applied Biosystems/Sciex API 300 instrument was equipped with a turboIon Spray source and a curtain gas interface while the Waters/Micromass Quattro Ultima instrument was characterized by its Z-spray source. Liquid chromatography/mass spectrometry analysis of native amino acids requires volatile ion-pairing mobile phase additives (mainly perfluorinated carboxylic acids). The effects of the structure and concentration of the ion-pairing reagents as well as the organic modifier percentage on the electrospray response of amino acids were studied in detail. The most favourable chromatographic conditions depend strongly on the mass spectrometer used. Several instrumental parameters were also studied, including spray voltage, transmission lens voltages, temperature of desolvation and auxiliary gas flow rates. The results show substantial qualitative differences depending on the instrument geometry. The quantitative performances of the two triple-quadrupole mass spectrometers were evaluated in terms of limits of detection and quantification. The effects of the matrix on the analyte ionization were also examined, and the long-term stability of the electrospray performance was studied over 12 h using a mobile phase containing the perfluorinated ion-pairing reagents. The study provides information on the robustness of the MS instrument and its detection sensitivity towards native amino acid analysis. It appears that each instrument has its good and bad points since one provides higher sensitivity while another is more robust.
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http://dx.doi.org/10.1002/jms.1287DOI Listing
February 2008

Analysis and validation of the phosphorylated metabolites of two anti-human immunodeficiency virus nucleotides (stavudine and didanosine) by pressure-assisted CE-ESI-MS/MS in cell extracts: sensitivity enhancement by the use of perfluorinated acids and alcohols as coaxial sheath-liquid make-up constituents.

Electrophoresis 2006 Jun;27(12):2464-76

Institut de Chimie Organique et Analytique (ICOA), Université d'Orléans, Orléans, France.

A CE method utilizing triple quadrupole electrospray (ES) MS (MS/MS) detection was developed and validated for the simultaneous measurement of nucleoside 5'-triphosphate and 5'-monophosphate anabolites of the anti-HIV (human immunodeficiency virus) didanosine (ddAMP, ddATP) and stavudine (d4TMP, d4TTP), among a pool of 14 endogenous 5'-mono-, di-, and triphosphate nucleosides. These compounds were spiked and extracted from peripheral blood mononuclear cells (PBMCs) which are the sites of HIV replication and drug action. An acetic acid/ammonia buffer (pH 10, ionic strength of 40 mM) was selected as running electrolyte, and the separation was performed by the simultaneous application of a CE voltage of +30 kV and an overimposed pressure of 28 mbar (0.4 psi). The application of pressure assistance was needed to provide stable ES conditions for successful coupling. The coupling was carried out with a modified sheath-flow interface, with one uninterrupted capillary (80 cmx 50 microm id; 192 microm od) in a dimension that fits into the ESI needle to get a stable ion spray. Some CE-MS parameters such as overimposed pressure, sheath-liquid composition, sheath-liquid and sheath-gas flow rates, ES voltage, and the CE capillary position were optimized in order to obtain an optimal sensitivity. The use of perfluorinated alcohols and acids in the coaxial sheath-liquid make-up (2,2,2-trifluoroethanol + 0.2 mM tridecafluoroheptanoic acid) appeared to provide the best MS sensitivity and improve the stability of spray. The linearity of the CE-MS and CE-MS/MS methods was checked under these conditions. Validation parameters such as accuracy, intraday and interday precision, and LOQs were determined in CE-MS/MS mode. Finally, the quantitation of d4T-TP and ddA-TP was validated in this CE-MS/MS system.
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http://dx.doi.org/10.1002/elps.200500850DOI Listing
June 2006

Validation of a real-time monitoring method for aniline in freshwater by high-performance liquid chromatography on porous graphitic carbon/electrospray ionization tandem mass spectrometry.

Rapid Commun Mass Spectrom 2004 ;18(14):1548-52

Institut de Chimie Organique et Analytique (ICOA), UMR 6005, Université d'Orléans, rue de Chartres. BP 6759, 45067 Orléans cedex 2, France.

Aniline is an anthropogenic organic compound widely used in polymer, rubber, pharmaceutical and dye industries but also used in biodegradability assays of chemical compounds as a positive biodegradation standard. By the two approaches, the rapid determination of aniline is necessary because of the high toxicity of aniline on hemoglobin. A high-performance liquid chromatography/tandem mass spectrometry (HPLC/MS/MS) method for the determination of aniline in water is described here. This method, using benzylamine as internal standard, was validated. No time-consuming sample preparation was needed. A rapid separation (7 min between two chromatographic runs) of aniline and benzylamine was performed on a Hypercarb porous graphitic carbon column using a gradient of methanol and 100 mM formic acid. The obtained limits of detection and quantification were 10 and 1 ng/mL, respectively. The response for aniline was quadratic. We show that this problem could be circumvented by showing that the [calculated concentration = f(introduced concentration)] function was linear. The linearity range was 10-1000 ng/mL. An example of an application consisting of an aniline 42-day degradation kinetic in water was demonstrated.
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http://dx.doi.org/10.1002/rcm.1526DOI Listing
August 2004
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