CNRS Biomolecules: Conception, Isolation, and Synthesis Laboratory

Paris, France

CNRS Biomolecules: Conception, Isolation, and Synthesis Laboratory

Paris, France

Time filter

Source Type

Lewin G.,CNRS Biomolecules: Conception, Isolation, and Synthesis Laboratory | MacIuk A.,CNRS Biomolecules: Conception, Isolation, and Synthesis Laboratory | Thoret S.,CNRS Natural Product Chemistry Institute | Aubert G.,CNRS Natural Product Chemistry Institute | And 2 more authors.
Journal of Natural Products | Year: 2010

Semisynthesis of 5,3'-dihydroxy-3,6,7,8,4'-pentamethoxyflavone (1), a natural flavone that binds with high affinity to tubulin, was performed from hesperidin, the very abundant Citrus flavanone, by a five-step sequence. The last step of the synthesis also gave rise to 5,3'-dihydroxy-3,6,7,4'- tetramethoxyflavone (= casticin or vitexicarpin) (10), 5,3'-dihydroxy-3,7,8,4'- tetramethoxyflavone (= gossypetin 3,7,8,4'-tetramethyl ether) (11), and, unexpectedly, 5,7,3'-trihydroxy-3,6,8,4'-tetramethoxyflavone (12) and 5,3'-dihydroxy-8-dimethylamino-3,6,7,4'-tetramethoxyflavone (= 8-dimethylaminocasticin) (13). Cytotoxicity and antitubulin activity of these five flavones, as well as 5,3'-dihydroxy-3,7,4'-trimethoxyflavone (= ayanin) (14) and intermediate 6,8-dibromo-ayanin (8), were evaluated. Comparison of the responses confirmed and clarified the influence of the A-ring substitution pattern on the biological activity. © 2010 The American Chemical Society and American Society of Pharmacognosy.


Pous J.,CNRS Natural Product Chemistry Institute | Courant T.,CNRS Natural Product Chemistry Institute | Bernadat G.,CNRS Biomolecules: Conception, Isolation, and Synthesis Laboratory | Iorga B.I.,CNRS Natural Product Chemistry Institute | And 2 more authors.
Journal of the American Chemical Society | Year: 2015

Chiral phosphoric acid-catalyzed asymmetric nitroso-Diels-Alder reaction of nitrosoarenes with carbamate-dienes afforded cis-3,6-disubstituted dihydro-1,2-oxazines in high yields with excellent regio-, diastereo-, and enantioselectivities. Interestingly, we observed that the catalyst is able not only to control the enantioselectivity but also to reverse the regioselectivity of the noncatalyzed nitroso-Diels-Alder reaction. The regiochemistry reversal and asynchronous concerted mechanism were confirmed by DFT calculations. © 2015 American Chemical Society.


Moal V.L.-L.,CNRS Biomolecules: Conception, Isolation, and Synthesis Laboratory | Moal V.L.-L.,Laboratory of Excellence in Research on Medication and Innovative Therapeutics | Moal V.L.-L.,University Paris - Sud | Servina A.L.,Laboratory of Excellence in Research on Medication and Innovative Therapeutics | Servina A.L.,University Paris - Sud
Microbiology and Molecular Biology Reviews | Year: 2013

Hosts are protected from attack by potentially harmful enteric microorganisms, viruses, and parasites by the polarized fully differentiated epithelial cells that make up the epithelium, providing a physical and functional barrier. Enterovirulent bacteria interact with the epithelial polarized cells lining the intestinal barrier, and some invade the cells. A better understanding of the cross talk between enterovirulent bacteria and the polarized intestinal cells has resulted in the identification of essential enterovirulent bacterial structures and virulence gene products playing pivotal roles in pathogenesis. Cultured animal cell lines and cultured human nonintestinal, undifferentiated epithelial cells have been extensively used for understanding the mechanisms by which some human enterovirulent bacteria induce intestinal disorders. Human colon carcinoma cell lines which are able to express in culture the functional and structural characteristics of mature enterocytes and goblet cells have been established, mimicking structurally and functionally an intestinal epithelial barrier. Moreover, Caco-2- derived M-like cells have been established, mimicking the bacterial capture property of M cells of Peyer's patches. This review intends to analyze the cellular and molecular mechanisms of pathogenesis of human enterovirulent bacteria observed in infected cultured human colon carcinoma enterocyte-like HT-29 subpopulations, enterocyte-like Caco-2 and clone cells, the colonic T84 cell line, HT-29 mucus-secreting cell subpopulations, and Caco-2-derived M-like cells, including cell association, cell entry, intracellular lifestyle, structural lesions at the brush border, functional lesions in enterocytes and goblet cells, functional and structural lesions at the junctional domain, and host cellular defense responses. Copyright © 2013, American Society for Microbiology. All Rights Reserved.


Servin A.L.,CNRS Biomolecules: Conception, Isolation, and Synthesis Laboratory | Servin A.L.,University Paris - Sud
Clinical Microbiology Reviews | Year: 2014

The pathogenicity and clinical pertinence of diffusely adhering Escherichia coli expressing the Afa/Dr adhesins (Afa/Dr DAEC) in urinary tract infections (UTIs) and pregnancy complications are well established. In contrast, the implication of intestinal Afa/Dr DAEC in diarrhea is still under debate. These strains are age de-pendently involved in diarrhea in children, are apparently not involved in diarrhea in adults, and can also be asymptomatic intestinal microbiota strainsin children and adult. This comprehensive review analyzes the epidemiology and diagnosis and highlights recent progress which has improved the understanding of Afa/Dr DAEC pathogenesis. Here,Isummarize the roles of Afa/Dr DAEC virulence factors, including Afa/Dr adhesins, flagella, Sat toxin, and pks island products, in the development of specific mechanisms of pathogenicity. In intestinal epithelial polarized cells, the Afa/Dr adhesins trigger cell membrane receptor clustering and activation of the linked cell signaling pathways, promote structural and functional cell lesions and injuries in intestinal barrier, induce proinflammatory responses, create angiogenesis, instigate epithelial-mesenchymal transition-like events, and lead to pks-dependent DNA damage. UTI-associated Afa/Dr DAEC strains, following adhesin-membrane receptor cell interactions and activation of associated lipid raft-dependent cell signaling pathways, internalize in a microtubule-dependent manner within urinary tract epithelial cells, develop a particular intracellular lifestyle, and trigger a toxin-dependent cell detachment. In response to Afa/Dr DAEC infection, the host epithelial cells generate antibacterial defense responses. Finally, I discuss a hypothetical role of intestinal Afa/Dr DAEC strains that can act as “silent pathogens” with the capacity to emerge as “pathobionts” for the development of inflammatory bowel disease and intestinal carcinogenesis. © 2014, American Society for Microbiology. All Rights Reserved.


Lievin-Le Moal V.,CNRS Biomolecules: Conception, Isolation, and Synthesis Laboratory | Lievin-Le Moal V.,Laboratory of Excellence in Research on Medication and Innovative Therapeutics | Lievin-Le Moal V.,University Paris - Sud | Servin A.L.,CNRS Biomolecules: Conception, Isolation, and Synthesis Laboratory | And 2 more authors.
Clinical Microbiology Reviews | Year: 2014

A vast and diverse array of microbial species displaying great phylogenic, genomic, and metabolic diversity have colonized the gastrointestinal tract. Resident microbes play a beneficial role by regulating the intestinal immune system, stimulating the maturation of host tissues, and playing a variety of roles in nutrition and in host resistance to gastric and enteric bacterial pathogens. The mechanisms by which the resident microbial species combat gastrointestinal pathogens are complex and include competitive metabolic interactions and the production of antimicrobial molecules. The human intestinal microbiota is a source from which Lactobacillus probiotic strains have often been isolated. Only six probiotic Lactobacillus strains isolated from human intestinal microbiota, i.e., L. rhamnosus GG, L. casei Shirota YIT9029, L. casei DN-114 001, L. johnsonii NCC 533, L. acidophilus LB, and L. reuteri DSM 17938, have been well characterized with regard to their potential antimicrobial effects against the major gastric and enteric bacterial pathogens and rotavirus. In this review, we describe the current knowledge concerning the experimental antibacterial activities, including antibiotic-like and cell-regulating activities, and therapeutic effects demonstrated in well-conducted, placebo-controlled, randomized clinical trials of these probiotic Lactobacillus strains. What is known about the antimicrobial activities supported by the molecules secreted by such probiotic Lactobacillus strains suggests that they constitute a promising new source for the development of innovative anti-infectious agents that act luminally and intracellularly in the gastrointestinal tract. © 2014, American Society for Microbiology. All Rights Reserved.


Maksimenko A.,University Paris - Sud | Alami M.,CNRS Biomolecules: Conception, Isolation, and Synthesis Laboratory | Zouhiri F.,University Paris - Sud | Brion J.-D.,CNRS Biomolecules: Conception, Isolation, and Synthesis Laboratory | And 7 more authors.
ACS Nano | Year: 2014

Drug delivery of combined cytotoxic and antivascular chemotherapies in multidrug nanoassemblies may represent an attractive way to improve the treatment of experimental cancers. Here we made the proof of concept of this approach on the experimental LS174-T human colon carcinoma xenograft nude mice model. Briefly, we have nanoprecipitated the anticancer compound gemcitabine conjugated with squalene (SQ-gem) together with isocombretastatin A-4 (isoCA-4), a new isomer of the antivascular combretastatin A-4 (CA-4). It was found that these molecules spontaneously self-assembled as stable nanoparticles (SQ-gem/isoCA-4 NAs) of ca. 142 nm in a surfactant-free aqueous solution. Cell culture viability tests and apoptosis assays showed that SQ-gem/isoCA-4 NAs displayed comparable antiproliferative and cytotoxic effects than those of the native gemcitabine or the mixtures of free gemcitabine with isoCA-4. Surprisingly, it was observed by confocal microscopy that the nanocomposites made of SQ-gem/isoCA-4 distributed intracellularly as intact nanoparticles whereas the SQ-gem nanoparticles remained localized onto the cell membrane. When used to deliver these combined chemotherapeutics to human colon cancer model, SQ-gem/isoCA-4 nanocomposites induced complete tumor regression (by 93%) and were found superior to all the other treatments, whereas the overall tolerance was better than the free drug treatments. This approach could be applied to other pairs of squalenoylated nanoassemblies with other non-water-soluble drugs, thus broadening the application of the "squalenoylation" concept in oncology. © 2014 American Chemical Society.


Nicolas V.,IFR 141 IPSIT | Nicolas V.,University Paris - Sud | Moal V.L.-L.,CNRS Biomolecules: Conception, Isolation, and Synthesis Laboratory | Moal V.L.-L.,LabEx LERMIT Laboratory of Excellence in Research on Medication | Moal V.L.-L.,University Paris - Sud
Infection and Immunity | Year: 2015

Both the endogenous antisecretory factor (AF) protein and peptide AF-16, which has a sequence that matches that of the active N-terminal region of AF, inhibit the increase in the epithelial transport of fluid and electrolytes induced by bacterial toxins in animal and ex vivo models. We conducted a study to investigate the inhibitory effect of peptide AF-16 against the increase of transcellular passage and paracellular permeability promoted by the secreted autotransporter toxin (Sat) in a cultured cellular model of the human intestinal epithelial barrier. Peptide AF-16 produced a concentration-dependent inhibition of the Sat-induced increase in the formation of fluid domes, in the mucosal-to-serosal passage of D-[1-14C]mannitol, and in the rearrangements in the distribution and protein expression of the tight junction (TJ)-associated proteins ZO-1 and occludin in cultured human enterocyte-like Caco-2/TC7 cell monolayers. In addition, we show that peptide AF-16 also inhibits the cholera toxin-induced increase of transcellular passage and the Clostridium difficile toxin-induced effects on paracellular permeability and TJ protein organization in Caco-2/TC7 cell monolayers. Treatment of cell monolayers by the lipid raft disorganizer methyl-β-cyclodextrin abolished the inhibitory activity of peptide AF-16 at the transcellular passage level and did not modify the effect of the peptide at the paracellular level. © 2015, American Society for Microbiology.


Thomas E.,CNRS Biomolecules: Conception, Isolation, and Synthesis Laboratory | Brion J.-D.,CNRS Biomolecules: Conception, Isolation, and Synthesis Laboratory | Peyrat J.-F.,CNRS Biomolecules: Conception, Isolation, and Synthesis Laboratory
European Journal of Medicinal Chemistry | Year: 2014

In an effort to develop novel vitamin D3 analogues, a series of aromatic compounds was synthetized, using efficient Negishi cross coupling between alkenylzinc reagents of the C,D-ring moiety of vitamin D3, and various substituted aromatic halides as A-ring mimics. The study aimed at exploring the influence of the replacement of the original vitamin D3 diene by a styrene unit on the biological activities. Potency in the induction of the differentiation of HL-60 cells for the lead compound 36 was 12 fold less important than calcitriol correlating with a weaker binding affinity for VDR. © 2014 Elsevier Masson SAS. All rights reserved.


Gravel E.,CEA Saclay Nuclear Research Center | Harfouche A.,CNRS Biomolecules: Conception, Isolation, and Synthesis Laboratory | Salame R.,CNRS Biomolecules: Conception, Isolation, and Synthesis Laboratory | Leblanc K.,CNRS Biomolecules: Conception, Isolation, and Synthesis Laboratory | And 2 more authors.
Chemistry - A European Journal | Year: 2013

Mixtures of tryptamine and reactive C5 units, presumably derived from lysine in nature, were studied to ascertain the spontaneous formation of the complex polycyclic alkaloid nitrarine. Several indolic compounds tracing the unified metabolism within the Nitraria genus were also characterized. Des mélanges de tryptamine et d'unités en C5 potentiellement dérivées de la lysine ont été étudiés et ont révélé la formation spontanée de la nitrarine, un alcaloïde polycyclique complexe, mais aussi de squelettes signant l'homogénéité surprenante du métabolisme secondaire dans le genre Nitraria. Just mix! The simple mixing of tryptamine and C5 units (presumably derived from L-lysine in nature) allowed the spontaneous formation of several indolic skeletons, including the unique structure of nitrarine (see scheme). Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.


Messaoudi S.,CNRS Biomolecules: Conception, Isolation, and Synthesis Laboratory | Brion J.-D.,CNRS Biomolecules: Conception, Isolation, and Synthesis Laboratory | Alami M.,CNRS Biomolecules: Conception, Isolation, and Synthesis Laboratory
Tetrahedron Letters | Year: 2011

The selective synthesis of N-(hetero)aryl-1-aminoindoles 3 from the corresponding N-aminoindoles and (hetero)aryl halides using a catalyst combination of Pd 2(dba) 3 associated to Josiphos is described. By switching to Xantphos as the ligand, the alternate catalytic system allows the coupling to proceed efficiently for the preparation of symmetrical and unsymmetrical N,N′-diaryl-1-aminoindole derivatives in good yields. © 2011 Elsevier Ltd. All rights reserved.

Loading CNRS Biomolecules: Conception, Isolation, and Synthesis Laboratory collaborators
Loading CNRS Biomolecules: Conception, Isolation, and Synthesis Laboratory collaborators