Nos tutelles

CNRS

Rechercher





Accueil > Les équipes > Chemical Biology (ChemBio) > Publications

Publications

publié le , mis à jour le

2022



  • V. Corcé, C. Ollivier, et L. Fensterbank, « Boron, silicon, nitrogen and sulfur-based contemporary precursors for the generation of alkyl radicals by single electron transfer and their synthetic utilization », Chemical Society Reviews, vol. 51, nᵒ 4, p. 1470-1510, févr. 2022.
    Résumé : Recent developments in the use of boron, silicon, nitrogen and sulfur derivatives in single-electron transfer reactions for the generation of alkyl radicals are described. Photoredox catalyzed, electrochemistry promoted or thermally-induced oxidative and reductive processes are discussed highlighting their synthetic scope and discussing their mechanistic pathways.
    Mots-clés : CHEMBIO, MACO, POLE 1, POLE 3.


  • C. Fayolle, P. Pigeon, N. Fischer-Durand, M. Salmain, O. Buriez, A. Vessières, et E. Labbé, « Synthesis, Electrochemical and Fluorescence Properties of the First Fluorescent Member of the Ferrocifen Family and of Its Oxidized Derivatives », Molecules, vol. 27, nᵒ 19, p. 6690, janv. 2022.
    Résumé : The first fluorescent ferrociphenol derivative (P797) has been synthesized via McMurry cross-coupling followed by copper-catalyzed [3 + 2] azide-alkyne cycloaddition of the fluorescent group coumarin. Cyclic voltammograms of P797 exhibit either a monoelectronic oxidation wave ascribed to the ferrocene Fe(II) → Fe(III) conversion or a three-electron oxidation process in the presence of a base, leading to a Fe(III) quinone methide adduct. This general sequence is consistent with those previously described for non-fluorescent ferrociphenols. Furthermore, the fluorescence properties of P797 and its oxidized intermediates appear to strongly depend on the redox state of the ferrocene group. Indeed, electrochemical generation of Fe(III) (ferrocenium) states markedly increases the fluorescence emission intensity. In contrast, the emission of the Fe(II) (ferrocene) states is partially quenched by photoinduced electron transfer (PET) from the Fe(II) donor to the coumarin acceptor and by concentration-dependent self-quenching. Owing to its switchable fluorescence properties, complex P797 could represent an innovative and useful tool to study the biodistribution and the redox state of ferrocifens in cancer cells.
    Mots-clés : CHEMBIO, coumarin, ferrocene, fluorescence switching, PET, POLE 3, redox state.
    Note Note


  • P. Idlas, A. Ladaycia, F. Némati, E. Lepeltier, P. Pigeon, G. Jaouen, D. Decaudin, et C. Passirani, « Ferrocifen stealth LNCs and conventional chemotherapy: a promising combination against multidrug-resistant ovarian adenocarcinoma », International Journal of Pharmaceutics, p. 122164, sept. 2022.
    Résumé : Ovarian cancer is one of the deadliest epithelial malignancies in women, owing to the multidrug resistance that restricts the success of conventional chemotherapy, carboplatin and paclitaxel. High grade serous ovarian carcinoma can be classified into two subtypes, the chemosensitive High OXPHOS and the Low OXPHOS tumour, less sensitive to chemotherapy. This difference of treatment efficacy could be explained by the redox status of these tumours, High OXPHOS exhibiting a chronic oxidative stress and an accumulation of reactive oxygen species. Ferrocifens, bio-organometallic compounds, are believed to be ROS producers with a good cytotoxicity on ovarian cancer cell lines. The aim of this study was to evaluate the in vivo efficacy of ferrocifen stealth lipid nanocapsules on High and Low OXPHOS ovarian Patient-Derived Xenograft models, alone or in combination to standard chemotherapy. Accordingly, two ferrocifens, P53 and P722, were encapsulated in stealth LNCs. The treatment by stealth P722-LNCs in combination with standard chemotherapy induced, with a concentration eight time lower than in stealth P53-LNCs, similar tumour reduction on a Low OXPHOS model, allowing us to conclude that P722 could be a leading ferrocifen to treat ovarian cancer. This combination of treatments may represent a promising synergistic approach to treat resistant ovarian adenocarcinoma.
    Mots-clés : CHEMBIO, Multidrug resistance, Nanoparticle, Organometallic compound, Ovarian cancer, Patient-Derived Xenograft model, POLE 3, ROS producer molecule.


  • Y. Mazouzi, F. Sallem, F. Farina, A. Loiseau, N. R. Tartaglia, M. Fontaine, A. Parikh, M. Salmain, C. Neri, et S. Boujday, « Biosensing Extracellular Vesicle Subpopulations in Neurodegenerative Disease Conditions », ACS Sensors, vol. 7, nᵒ 6, p. 1657-1665, juin 2022.
    Résumé : Extracellular vesicles (EVs) are secreted nanoparticles that are involved in intercellular communication and that modulate a wide range of biological processes in normal and disease conditions. However, EVs are highly heterogeneous in terms of origin in the cell, size, and density. As a result, complex protocols are required to identify and characterize specific EV subpopulations, limiting biomedical applications, notably in diagnostics. Here, we show that combining quartz crystal microbalance with dissipation (QCM-D) and nanoplasmonic sensing (NPS) provides a facile method to track the viscoelastic properties of small EVs. We applied this multisensing strategy to analyze small EVs isolated by differential ultracentrifugation from knock-in mouse striatal cells expressing either a mutated allele or wild-type allele of huntingtin (Htt), the Huntington’s disease gene. Our results validate the sensing strategy coupling QCM-D and NPS and suggest that the mass and viscoelastic dissipation of EVs can serve as potent biomarkers for sensing the intercellular changes associated with the neurodegenerative condition.
    Mots-clés : CHEMBIO, POLE 3.


  • M. Nicolas, B. Beito, M. Oliveira, M. Tudela Martins, B. Gallas, M. Salmain, S. Boujday, et V. Humblot, « Strategies for Antimicrobial Peptides Immobilization on Surfaces to Prevent Biofilm Growth on Biomedical Devices », Antibiotics, vol. 11, nᵒ 1, p. 13, janv. 2022.
    Résumé : Nosocomial and medical device-induced biofilm infections affect millions of lives and urgently require innovative preventive approaches. These pathologies have led to the development of numerous antimicrobial strategies, an emergent topic involving both natural and synthetic routes, among which some are currently under testing for clinical approval and use. Antimicrobial peptides (AMPs) are ideal candidates for this fight. Therefore, the strategies involving surface functionalization with AMPs to prevent bacterial attachment/biofilms formation have experienced a tremendous development over the last decade. In this review, we describe the different mechanisms of action by which AMPs prevent bacterial adhesion and/or biofilm formation to better address their potential as anti-infective agents. We additionally analyze AMP immobilization techniques on a variety of materials, with a focus on biomedical applications. Furthermore, we summarize the advances made to date regarding the immobilization strategies of AMPs on various surfaces and their ability to prevent the adhesion of various microorganisms. Progress toward the clinical approval of AMPs in antibiotherapy is also reviewed.
    Mots-clés : AMP, antimicrobial, biofilms, biofunctionalization, CHEMBIO, immobilization, peptide, POLE 3.


  • J. Sanz Garcia, M. Gaschard, I. Navizet, M. Sahihi, S. Top, Y. Wang, P. Pigeon, A. Vessières, M. Salmain, et G. Jaouen, « Inhibition of cathepsin B by ferrocenyl indenes highlights a new pharmacological facet of ferrocifens », European Journal of Inorganic Chemistry, vol. 2022, nᵒ 9, janv. 2022.
    Résumé : The family of ferrocifens initially built up from the anti-estrogen tamoxifen shows a broad antitumor activity both  in vitro  and  in vivo . Their mechanism of action relies on the presence of the redox motif [ferrocene-ene-phenol] that, under oxidative conditions, generates reactive oxygen species (ROS) and affords electrophilic quinone methides (QMs) having the ability to alkylate biological nucleophiles and in turn elicit a strong antiproliferative activity. In this context, the cysteine protease cathepsin B was initially presumed to be a target for ferrocenyl QMs.  In vitro  enzymatic assays ruled out this hypothesis but unexpectedly revealed that other ferrocifen metabolites, i.e. ferrocenyl indenes, acted as moderate inhibitors of cathepsin B. These experimental results were nicely confirmed by molecular docking calculations, that showed that the monophenol ferrocenyl indene and to a lower extent the diphenol interacted with the active site of cathepsin B, making it an unanticipated target of ferrocifens.
    Mots-clés : antitumor agent, bioorganometallic chemistry, CHEMBIO, computational chemistry, cysteine protease, docking, POLE 3.


  • M. Soroush, W. Ait Mammar, A. Wilson, H. Ghourchian, M. Salmain, et S. Boujday, « Design and Optimization of a Magneto-Plasmonic Sandwich Biosensor for Integration within Microfluidic Devices », Biosensors, vol. 12, nᵒ 10, p. 799, oct. 2022.
    Résumé : We designed a magneto-plasmonic biosensor for the immunodetection of antigens in minute sample volume. Both spherical gold nanoparticles (AuNP) and magnetic beads (MB) were conjugated to goat anti-rabbit IgG antibody (Ab) capable of recognizing a model target, rabbit IgG (rIgG). The AuNP bioconjugate was used as the optical detection probe while the MB one was used as the capture probe. Addition of the target analyte followed by detection probe resulted in the formation of a sandwich immunocomplex which was separated from the unbound AuNP-Ab conjugate by application of an external magnetic field. The readout was executed either in a direct or in indirect way by measuring the UV–Visible spectrum of each fraction in a specially designed microcell. Dose–response curves were established from the optical signal of the immunocomplex and unbound AuNP-Ab conjugate fractions. Finally, the assay was transposed to a microfluidic cell specially designed to enable easy separation of the immunocomplex and AuNP-Ab conjugate fractions and subsequent analysis of the latter fraction and achieve the quantification of the analyte in the ng/mL concentration range.
    Mots-clés : CHEMBIO, gold nanoparticles, immunosensor, magnetic beads, microfluidic chip, optical transduction, POLE 3.


  • F. Zhao, M. Abdellaoui, W. Hagui, M. Ballarin-Marion, J. Berthet, V. Corcé, S. Delbaere, H. Dossmann, A. Espagne, J. Forté, L. Jullien, T. Le Saux, V. Mouriès-Mansuy, C. Ollivier, et L. Fensterbank, « Reactant-induced photoactivation of in situ generated organogold intermediates leading to alkynylated indoles via Csp2-Csp cross-coupling », Nature Communications, vol. 13, nᵒ 1, p. 2295, avr. 2022.
    Résumé : Photosensitization of organogold intermediates is an emerging field in catalysis. In this context, an access to 2,3-disubstituted indoles from o-alkynyl aniline and iodoalkyne derivatives via a gold-catalyzed sequence under visible-light irradiation and in the absence of an exogenous photocatalyst was uncovered. A wide scope of the process is observed. Of note, 2-iodo-ynamides can be used as electrophiles in this cross-coupling reaction. The resulting N-al

    kynyl indoles lend themselves to post-functionalization affording valuable scaffolds, notably benzo[a]carbazoles. Mechanistic studies converge on the fact that a potassium sulfonyl amide generates emissive aggregates in the reaction medium. Static quenching of these aggregates by a vinylgold(I) intermediate yields to an excited state of the latter, which can react with an electrophile via oxidative addition and reductive elimination to forge the key C-C bond. This reactant-induced photoactivation of an organogold intermediate opens rich perspectives in the field of cross-coupling reactions.
    Mots-clés : CHEMBIO, CSOB, Photocatalysis, POLE 1, POLE 3, Reaction mechanisms.

2021



  • L. Chang, N. Fischer-Durand, G. Gontard, B. Bertrand, S. Thorimbert, et L. Dechoux, « A solvent-free, catalyst-free formal [3+3] cycloaddition dearomatization strategy: towards new fluorophores for biomolecules labelling », ChemSusChem, vol. 14, nᵒ 8, p. 1821-1824, 2021.
    Résumé : A general, sustainable dearomatization reaction for nitrogen-containing heterocycles was developed. Under solvent free conditions and without catalyst, the biorenewable methyl coumalate ( MC ) reacts as an efficient C3 partner to convert eleven types of basic aromatic rings into their pyrido[1,2-a] fused derivatives in good to excellent yields. The fluorescence properties of some of the products were harnessed to conjugate fluorescent tags to BSA and immunoglobulin G.
    Mots-clés : CHEMBIO, dearomatization reaction, fluorescent probes, methyl coumalate, Michael addition, Nitrogen heterocycles, POLE 3.


  • S. Khodjoyan, E. Remadna, H. Dossmann, D. Lesage, G. Gontard, J. Forté, H. Hoffmeister, U. Basu, I. Ott, P. Spence, Z. Waller, M. Salmain, et B. Bertrand, « [(C^C)Au(N^N)]+ complexes as a new family of anticancer candidates: synthesis, characterization and exploration of the antiproliferative properties », Chemistry – A European Journal, vol. 27, nᵒ 63, p. 15773-15785, 2021.
    Résumé : A library of eleven cationic gold(III) complexes of the general formula [(C^C)Au(N^N)] + when C^C is either biphenyl or 4,4’-ditertbutyldiphenyl and N^N is a bipyridine, phenanthroline or dipyridylamine derivative have been synthesized and characterized. Contrasting effects on the viability of the triple negative breast cancer cells MDA-MB-231 was observed from a preliminary screening. The antiproliferative activity of the seven most active complexes were further assayed on a larger panel of human cancer cells as well as on non-cancerous cells for comparison. Two complexes stood out for being either highly active or highly selective. Eventually, reactivity studies with biologically meaningful amino acids, glutathione, higher order DNA structures and thioredoxin reductase (TrxR) revealed a markedly different behavior from that of the well-known coordinatively isomeric [(C^N^C)Au(NHC)] + structure. This makes the [(C^C)Au(N^N)] + complexes a new class of organogold compounds with an original mode of action.
    Mots-clés : Bioorganometallics, Biphenyl, Cancer, Chelate, CHEMBIO, CSOB, Gold, POLE 3.


  • E. Levernier, K. Jaouadi, H. - R. Zhang, V. Corcé, A. Bernard, G. Gontard, C. Troufflard, L. Grimaud, E. Derat, C. Ollivier, et L. Fensterbank, « Phenyl Silicates with Substituted Catecholate Ligands: Synthesis, Structural Studies and Reactivity », Chemistry – A European Journal, vol. 27, nᵒ 34, p. 8782-8790, 2021.
    Résumé : While the generation of aryl radicals by photoredox catalysis under reductive conditions is well documented, it has remained challenging under an oxidative pathway. Because of the easy photo-oxidation of alkyl bis-catecholato silicates, a general study of phenyl silicates bearing substituted catecholate ligands has been achieved. The newly synthesized phenyl silicates have been fully characterized, and their reactivity has been explored. It was found that, thanks to the substitution of the catecholate moiety, notably with the 4-cyanocatecholato ligand, the phenyl radical could be generated and trapped. Computational studies provided a rationale for these findings.
    Mots-clés : aryl radicals, CHEMBIO, MACO, oxidation, photoredox catalysis, POLE 1, POLE 3, silicates.

2020



  • Abdmouleh, Fatma, El Arbi, Mehdi, Hajer, Ben Saad, Jellali, Karim, Etata, Emna, Amara, Ibtissem Ben, Pigeon, Pascal, Hanen, Ben Hassen, Top, Siden, Jaouen, Gérard, Hammami, Riadh, Mamdouh, Ben Ali, et Gupta, Girish Kumar, « Antimicrobial, Antitumor and Side Effects Assessment of a Newly Synthesized Tamoxifen Analog », Current Topics in Medicinal Chemistry, vol. 20, nᵒ 25, p. 2281-2288, sept. 2020.
    Résumé : Background: Tamoxifen citrate is a very prevalent drug marketed under several trade names like Apo-Tamox, Nolvadex, Tamec, Tamizam, and Tamoplex. This molecule is approved by the FDA for breast cancer treatment. Some studies have shown that tamoxifen has anti-tuberculosis and antiparasitic activities. Like any drug, tamoxifen possesses side effects, more or less dangerous. Aims: Basically, this work is a comparative study that aims to: primarily compare the antimicrobial and antitumor activities of tamoxifen and a newly synthesized tamoxifen analog; and to determine the molecule with lesser side effects. Methods: Three groups of mice were injected with tamoxifen citrate and compound 2(1,1-bis[4-(3- dimethylaminopropoxy)phenyl]-2-phenyl-but-1-ene dihydrochloride) at doses corresponding to C1 (1/10), C2 (1/50), and C3 (1/100) to compound 2 lethal dose (LD50 = 75 mg/kg) administered to adult mice. A group of noninjected mice served as a study control. Results: Experimental results suggest that compound 2 has better antitumor and antimicrobial activity than tamoxifen citrate besides its lower toxicity effects. Conclusion: The results obtained from the present study confirmed the antitumor and antimicrobial effect of tamoxifen citrate and its hematological side effects. Compound 2 seems to be more effective than tamoxifen citrate for antitumor and antimicrobial treatment while having less hematological side effects and less disruption of the blood biochemical parameters. These findings encourage us to perform further studies on compound 2 and test it for other therapeutic uses for which tamoxifen was found effective.
    Mots-clés : CHEMBIO, POLE 3.
--- Exporter la sélection au format


Test d’affichage de la liste par Hal