Author: "Romain Haudecoeur" - Searchworks@Jio Institute Digital Library Search Results

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33 results on '"Romain Haudecoeur"'

1. Design and Synthesis of Novel Amino and Acetamidoaurones with Antimicrobial Activities

Author: Attilio Di Maio, Hamza Olleik, Elise Courvoisier-Dezord, Sophie Guillier, Fabienne Neulat-Ripoll, Romain Haudecoeur, Jean-Michel Bolla, Magali Casanova, Jean-François Cavalier, Stéphane Canaan, Valérie Pique, Yolande Charmasson, Elias Baydoun, Akram Hijazi, Josette Perrier, Marc Maresca, and Maxime Robin
Subjects: aurone, anti-bacterial agents, cytotoxicity tests, structure-activity relationship, Therapeutics. Pharmacology, RM1-950
Abstract: The development of new and effective antimicrobial compounds is urgent due to the emergence of resistant bacteria. Natural plant flavonoids are known to be effective molecules, but their activity and selectivity have to be increased. Based on previous aurone potency, we designed new aurone derivatives bearing acetamido and amino groups at the position 5 of the A ring and managing various monosubstitutions at the B ring. A series of 31 new aurone derivatives were first evaluated for their antimicrobial activity with five derivatives being the most active (compounds 10, 12, 15, 16, and 20). The evaluation of their cytotoxicity on human cells and of their therapeutic index (TI) showed that compounds 10 and 20 had the highest TI. Finally, screening against a large panel of pathogens confirmed that compounds 10 and 20 possess large spectrum antimicrobial activity, including on bioweapon BSL3 strains, with MIC values as low as 0.78 µM. These results demonstrate that 5-acetamidoaurones are far more active and safer compared with 5-aminoaurones, and that benzyloxy and isopropyl substitutions at the B ring are the most promising strategy in the exploration of new antimicrobial aurones.
Published: 2024
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2. Synthetic G-Quartets as Versatile Nanotools for the Luminescent Detection of G-Quadruplexes

Author: Aurelien Laguerre, Marine Levillain, Loic Stefan, Romain Haudecoeur, Fares Katranji, Marc Pirrotta, and David Monchaud
Subjects: Dota, G-quadruplexes, Luminescence, Pyrene, Tasq, Terbium, Chemistry, QD1-999
Abstract: Recent years have witnessed a tremendous increase in the biotechnological applications of nucleic acid-based nanotools. Beyond their biological relevance, nucleobases have indeed found new scopes of applications in bionanotechnology, which are expanding nowadays at an accelerated pace. Among the four canonical nucleobases (adenine, guanine, cytosine and thymine), guanine is certainly the most useful and used base, thanks to its versatile H-bond donating/accepting properties that make it suitable for being involved in various assemblies ranging from base-pairs to base-quartets. Here, we would like to report on an innovative guanine-based molecular tool named Tb. Pyro-DOTASQ: this metal complex has a sophisticated chemical structure that allows formation of an intramolecular G-quartet upon interaction with alternative secondary structures known as G-quadruplexes. This target-promoted molecular switch triggers a luminescence response that would permit the use of Tb. Pyro-DOTASQ to search and detect quadruplex-forming DNA and RNA sequences: its unique design indeed allows it i) to create specific interaction with quadruplexes, ii) to provide an easily readable luminescent output to monitor this association and iii) to be readily immobilized on graphene surface, thus making Tb. Pyro-DOTASQ a high-value molecular device. Results obtained in the course of in-depth biophysical analyses raise questions about the actual supramolecular structure of Tb. Pyro-DOTASQ: these results thus shed a bright light on the care that must be exercised when using intricate molecular architectures to construct elaborated supramolecular metal complexes.
Published: 2015
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3. Bioactive Aurones, Indanones, and Other Hemiindigoid Scaffolds: Medicinal Chemistry and Photopharmacology Perspectives

Author: Leticia M. Lazinski, Guy Royal, Maxime Robin, Marc Maresca, Romain Haudecoeur, Université Grenoble Alpes (UGA), Aix Marseille Université (AMU), Institut méditerranéen de biodiversité et d'écologie marine et continentale (IMBE), Avignon Université (AU)-Aix Marseille Université (AMU)-Institut de recherche pour le développement [IRD] : UMR237-Centre National de la Recherche Scientifique (CNRS), ANR-17-EURE-0003,CBH-EUR-GS,CBH-EUR-GS(2017), ANR-19-CE44-0002,EPIDERMIS,Vers des sondes et inhibiteurs conçus pour interagir avec hsTY : une voie vers la suppression de la mélanogénèse in vivo(2019), Département de pharmacochimie moléculaire (DPM), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Département de Chimie Moléculaire (DCM), Institut des Sciences Moléculaires de Marseille (ISM2), and Aix Marseille Université (AMU)-École Centrale de Marseille (ECM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Inhibitors, Chemistry, Pharmaceutical, [SDV]Life Sciences [q-bio], Reaction products, Peptides and proteins, [CHIM.THER]Chemical Sciences/Medicinal Chemistry, Ligands, Tubulin Modulators, Indans, Drug Discovery, Acetylcholinesterase, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, Molecular Medicine, Selectivity, Cholinesterase Inhibitors, Benzofurans, Fluorescent Dyes, Inhibition
Abstract: International audience; Hemiindigoids comprise a range of natural and synthetic scaffolds that share the same aromatic hydrocarbon backbone as well as promising biological and optical properties. The encouraging therapeutic potential of these scaffolds has been unraveled by many studies over the past years and uncovered representants with inspiring pharmacophoric features such as the acetylcholinesterase inhibitor donezepil and the tubulin polymerization inhibitor indanocine. In this review, we summarize the last advances in the medicinal potential of hemiindigoids, with a special attention to molecular design, structure–activity relationship, ligand-target interactions, and mechanistic explanations covering their effects. As their strong fluorogenic potential and photoswitch behavior recently started to be highlighted and explored in biology, giving rise to the development of novel fluorescent probes and photopharmacological agents, we also discuss these properties in a medicinal chemistry perspective.
Published: 2022
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4. Resorcinol-based hemiindigoid derivatives as human tyrosinase inhibitors and melanogenesis suppressors in human melanoma cells

Author: Brayan Roulier, Inbal Rush, Leticia M. Lazinski, Basile Pérès, Hamza Olleik, Guy Royal, Ayelet Fishman, Marc Maresca, Romain Haudecoeur, Institut des Sciences Moléculaires de Marseille (ISM2), Aix Marseille Université (AMU)-École Centrale de Marseille (ECM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Université Grenoble Alpes (UGA), Technion - Israel Institute of Technology [Haifa], ANR-11-LABX-0003,ARCANE,Grenoble, une chimie bio-motivée(2011), and ANR-19-CE44-0002,EPIDERMIS,Vers des sondes et inhibiteurs conçus pour interagir avec hsTY : une voie vers la suppression de la mélanogénèse in vivo(2019)
Subjects: Hemiindigoid, Indanone, Pharmacology, Melanogenesis, [SDV]Life Sciences [q-bio], Organic Chemistry, Drug Discovery, [CHIM]Chemical Sciences, Aurone, human Tyrosinase, General Medicine, human Tyrosinase Hemiindigoid Melanogenesis Melanoma Aurone Indanone, Melanoma
Abstract: International audience; Human tyrosinase (hsTYR) catalyzes the key steps of melanogenesis, making it a privileged target for reducing melanin production in vivo. However, very few hsTYR inhibitors have been reported so far in the literature, whereas thousands of mushroom tyrosinase (abTYR) inhibitors are known. Yet, as these enzymes are actually very different, including at their active sites, there is an urgent need for new true hsTYR inhibitors in order to enable human-directed pharmacological and dermocosmetic applications without encountering the inefficiency and toxicity issues currently triggered by kojic acid or hydroquinone. Starting from the two most active compounds reported to date, i.e. a 2-hydroxypyridine-embedded aurone and thiamidol, we combined herein key structural elements and developed new nanomolar hsTYR inhibitors with cell-based activity. From a complete series of thirty-eight synthesized derivatives, excellent inhibition values were obtained for two compounds in both human melanoma cell lysates and purified hsTYR assays, and a promising improvement was observed in whole cell experiments.
Published: 2022
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5. β-Carboline as a Privileged Scaffold for Multitarget Strategies in Alzheimer’s Disease Therapy

Author: Anthonin Gori, Aurélien Beato, Benjamin Boucherle, Marine Peuchmaur, and Romain Haudecoeur
Subjects: Scaffold, Amyloid β, Context (language use), Disease, 01 natural sciences, Structure-Activity Relationship, 03 medical and health sciences, chemistry.chemical_compound, Disease therapy, Alzheimer Disease, Drug Discovery, Animals, Humans, 030304 developmental biology, Neurotransmitter Agents, 0303 health sciences, Molecular interactions, Acetylcholinesterase, 3. Good health, 0104 chemical sciences, 010404 medicinal & biomolecular chemistry, chemistry, Drug Design, Molecular Medicine, Neuroscience, Carbolines
Abstract: The natural β-carboline alkaloids display similarities with neurotransmitters that can be favorably exploited to design bioactive and bioavailable drugs for Alzheimer's disease (AD) therapy. Several AD targets are currently and intensively being investigated, divided in different hypotheses: mainly the cholinergic, the amyloid β (Aβ), and the Tau hypotheses. To date, only symptomatic treatments are available involving acetylcholinesterase and NMDA inhibitors. On the basis of plethoric single-target structure-activity relationship studies, the β-carboline scaffold was identified as a powerful tool for fostering activity and molecular interactions with a wide range of AD-related targets. This knowledge can undoubtedly be used to design multitarget-directed ligands, a highly relevant strategy preferred in the context of multifactorial pathology with intricate etiology such as AD. In this review, we first individually discuss the AD targets of the β-carbolines, and then we focus on the multitarget strategies dedicated to the deliberate design of new efficient scaffolds.
Published: 2021
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6. Advances in the Design of Genuine Human Tyrosinase Inhibitors for Targeting Melanogenesis and Related Pigmentations

Author: Brayan Roulier, Romain Haudecoeur, and Basile Pérès
Subjects: Tyrosinase, Skin Lightening Preparations, Pigmentations, Computational biology, 01 natural sciences, Protein Structure, Secondary, Biological Factors, 03 medical and health sciences, Melanin synthesis, Drug Delivery Systems, Drug Discovery, Humans, Amino Acid Sequence, Enzyme Inhibitors, Melanoma, 030304 developmental biology, Melanins, 0303 health sciences, Monophenol Monooxygenase, Pigmentation, Chemistry, Recombinant expression, Depigmenting agents, 3. Good health, 0104 chemical sciences, 010404 medicinal & biomolecular chemistry, Drug Design, Melanocytes, Molecular Medicine, Mushroom tyrosinase, Agaricales
Abstract: Human tyrosinase (hsTYR) is the key enzyme ensuring the conversion of l-tyrosine to dopaquinone, thereby initiating melanin synthesis, i.e., melanogenesis. Although the protein has long been familiar, knowledge about its three-dimensional structure and efficient overexpression protocols emerged only recently. Consequently, for decades medicinal chemistry studies aiming at developing skin depigmenting agents relied almost exclusively on biological assays performed using mushroom tyrosinase (abTYR), producing a plethoric literature, often of little useful purpose. Indeed, several recent reports have pointed out spectacular differences in terms of interaction patterns and inhibition values between hsTYR and abTYR, including for widely used standard tyrosinase inhibitors. In this review, we summarize the last developments regarding the potential role of hsTYR in human pathologies, the advances in recombinant expression systems and structural data retrieving, and the pioneer generation of true hsTYR inhibitors. Finally, we present suggestions for the design of future inhibitors of this highly attractive target in pharmacology and dermocosmetics.
Published: 2020
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7. Targeting different binding sites in the CFTR structures allows to synergistically potentiate channel activity

Author: Sandra Mirval, Nesrine Baatallah, Jean-Paul Mornon, Julien Alliot, Isabelle Callebaut, Wael Zeinyeh, Arnaud Billet, Brice Hoffmann, Pierre Lehn, Ahmad Elbahnsi, Frédéric Becq, Renaud Zelli, Christophe Simard, Jean-Luc Décout, Romain Haudecoeur, Antoine Fortuné, Benjamin Boucherle, Benoit Chevalier, Alexandre Hinzpeter, Lionel Froux, Signalisation et Transports Ioniques Membranaires (STIM), Université de Poitiers-Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS), Institut de minéralogie, de physique des matériaux et de cosmochimie (IMPMC), Muséum national d'Histoire naturelle (MNHN)-Institut de recherche pour le développement [IRD] : UR206-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Université Grenoble Alpes (UGA), Institut Necker Enfants-Malades (INEM - UM 111 (UMR 8253 / U1151)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Université de Paris - UFR Médecine Paris Centre [Santé] (UP Médecine Paris Centre), Université de Paris (UP), Génétique, génomique fonctionnelle et biotechnologies (UMR 1078) (GGB), EFS-Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO), Université de Poitiers-Université de Tours-Centre National de la Recherche Scientifique (CNRS), Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO)-Université de Brest (UBO)-EFS-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Université Paris Cité - UFR Médecine [Santé] (UPCité UFR Médecine), Université Paris Cité (UPCité), HAL-SU, Gestionnaire, UFR Médecine [Santé] - Université Paris Cité (UFR Médecine UPCité), and ANR-17-EURE-0003,CBH-EUR-GS,CBH-EUR-GS(2017)
Subjects: Mutant, Modulator, Cystic Fibrosis Transmembrane Conductance Regulator, Quinolones, Aminophenols, 3D structure, Cystic fibrosis, Combinatorial therapies, Ivacaftor, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Drug Discovery, medicine, Humans, Binding site, CFTR, 030304 developmental biology, Pharmacology, Ussing chamber, 0303 health sciences, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Forskolin, Binding Sites, biology, Organic Chemistry, Drug Synergism, General Medicine, Potentiator, medicine.disease, Small molecule, Cystic fibrosis transmembrane conductance regulator, 3. Good health, Cell biology, Molecular Docking Simulation, chemistry, Purines, 030220 oncology & carcinogenesis, Benzamides, Mutation, biology.protein, Halide-sensitive fluorescence, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, medicine.drug, HeLa Cells, Protein Binding
Abstract: International audience; Recent evidence shows that combination of correctors and potentiators, such as the drug ivacaftor (VX-770), can significantly restore the functional expression of mutated Cystic Fibrosis Transmembrane conductance Regulator (CFTR), an anion channel which is mutated in cystic fibrosis (CF). The success of these combinatorial therapies highlights the necessity of identifying a broad panel of specific binding mode modulators, occupying several distinct binding sites at structural level. Here, we identified two small molecules, SBC040 and SBC219, which are two efficient cAMP-independent potentiators, acting at low concentration of forskolin with EC50 close to 1 μM and in a synergic way with the drug VX-770 on several CFTR mutants of classes II and III. Molecular dynamics simulations suggested potential SBC binding sites at the vicinity of ATP-binding sites, distinct from those currently proposed for VX-770, outlining SBC molecules as members of a new family of potentiators.
Published: 2020
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8. A One-Pot Synthesis of Highly Functionalized Purines

Author: Romain Haudecoeur, Julien Alliot, Jean-Luc Décout, Benjamin Boucherle, Renaud Zelli, Isabelle Callebaut, and Wael Zeinyeh
Subjects: Peptide nucleic acid, 010405 organic chemistry, Organic Chemistry, One-pot synthesis, 010402 general chemistry, 01 natural sciences, Biochemistry, 0104 chemical sciences, chemistry.chemical_compound, chemistry, Reagent, Rapid access, Nucleic acid, Organic chemistry, Physical and Theoretical Chemistry, Purine metabolism, High potential
Abstract: Highly substituted purines were synthesized in good to high yields through a one-pot straightforward metal-free scalable method, using the Traube synthesis adapted to Vilsmeier-type reagents. From 5-amino-4-chloropyrimidines, new 9-aryl-substituted chloropurines and intermediates for peptide nucleic acid synthesis were prepared. Variant procedures allowing a rapid synthesis of ribonucleosides and 7-benzylpurine from 5-amidino-6-aminopyrimidines are also reported to illustrate the high potential of this versatile toolbox. This route appears to be particularly interesting in the field of nucleic acids for a direct and rapid access to various new 8-alkylpurine nucleosides.
Published: 2017
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9. Occurrences, biosynthesis and properties of aurones as high-end evolutionary products

Author: Benjamin Boucherle, Romain Haudecoeur, Marine Peuchmaur, and Ahcène Boumendjel
Subjects: Flavonoids, Biological Products, Molecular Structure, 010405 organic chemistry, Chemistry, Anacardiaceae, Rhamnaceae, fungi, food and beverages, Fabaceae, Flowers, Plant Science, General Medicine, Horticulture, Bioinformatics, 01 natural sciences, Biochemistry, 0104 chemical sciences, 010404 medicinal & biomolecular chemistry, Evolutionary biology, Identification (biology), Molecular Biology, Benzofurans, Sulfuretin
Abstract: Recent years have witnessed a considerable renewed interest for the uncommon flavonoid class of aurones. The characterization of two major biosynthetic machineries involved in their biosynthesis in flowers has encouraged the revival of phytochemical studies and identification of original structures, a process started almost seventy-five years ago. This review draws up an exhaustive map of natural occurrences of aurones their biosynthetic pathways and roles, with the aim to link their original structural properties among flavonoids to their place in evolution and the selective advantages they bring to some of the most advanced taxa in the plant kingdom.
Published: 2017
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10. Aurone derivatives as promising antibacterial agents against resistant Gram-positive pathogens

Author: Basile Pérès, Marc Maresca, Hamza Olleik, Akram Hijazi, Josette Perrier, Samir Yahiaoui, Ahcène Boumendjel, Elias Baydoun, Brayan Roulier, Elise Courvoisier-Dezord, Romain Haudecoeur, Josette Raymond, Institut des Sciences Moléculaires de Marseille (ISM2), Aix Marseille Université (AMU)-École Centrale de Marseille (ECM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Physique et mécanique des milieux hétérogenes (UMR 7636) (PMMH), Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Institut de Chimie de Strasbourg, Centre National de la Recherche Scientifique (CNRS)-Université Louis Pasteur - Strasbourg I-Institut de Chimie du CNRS (INC), American University of Beirut [Beyrouth] (AUB), Université Paris Descartes - Paris 5 (UPD5), Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Département de pharmacochimie moléculaire (DPM ), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Université Louis Pasteur - Strasbourg I-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), ANR-17-EURE-0003,CBH-EUR-GS,CBH-EUR-GS(2017), Aix Marseille Université (AMU)-École Centrale de Marseille (ECM)-Centre National de la Recherche Scientifique (CNRS), Physique et mécanique des milieux hétérogenes (PMMH), Centre National de la Recherche Scientifique (CNRS)-ESPCI ParisTech-Université Paris Diderot - Paris 7 (UPD7)-Université Pierre et Marie Curie - Paris 6 (UPMC), Université Louis Pasteur - Strasbourg I-Centre National de la Recherche Scientifique (CNRS), CHU Cochin [AP-HP], Département de pharmacochimie moléculaire (DPM), and Université Grenoble Alpes (UGA)-Université Joseph Fourier - Grenoble 1 (UJF)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Methicillin-Resistant Staphylococcus aureus, [CHIM.THER]Chemical Sciences/Medicinal Chemistry, Selective inhibition, Gram-Positive Bacteria, 01 natural sciences, Microbiology, 03 medical and health sciences, chemistry.chemical_compound, Structure-Activity Relationship, Therapeutic index, Drug Discovery, Aurone, Cytotoxicity, 030304 developmental biology, Gram, Benzofurans, Pharmacology, 0303 health sciences, biology, 010405 organic chemistry, Chemistry, Organic Chemistry, Cell Membrane, General Medicine, biology.organism_classification, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, 3. Good health, 0104 chemical sciences, Anti-Bacterial Agents, Pseudomonas aeruginosa, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, Antibacterial activity, Bacteria
Abstract: International audience; A set of variously substituted aurones was synthesized and evaluated against Methicillin-Resistant S. aureus (MRSA) and P. aeruginosa. Several analogues were found active against MRSA, but no effect was recorded against P. aeruginosa. Compounds 27, 30 and 33 showed low cytotoxicity, and were tested against a full range of bacterial (Gram-positive and Gram-negative) and fungal species, including resistant strains. These aurones displayed a selective inhibition of Gram-positive bacteria with excellent Therapeutic Index values, while showing no significant action on several Gram-negative strains, H. pylori and V. alginolyticus being the only susceptible strains among the Gram-negative bacteria tested. A per-meabilization assay showed that the antibacterial activity of at least some of the aurones could be linked to alterations of the bacterial membrane. Overall, this study endorses the use of the aurone scaffold for the development of new potent and selective antibacterial agents.
Published: 2018
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11. Piperidinyl-embeded chalcones possessing anti PI3Kδ inhibitory properties exhibit anti-atopic properties in preclinical models

Author: Charles Dumontet, Fabrice Gardebien, Guillaume Beck, Alessandra Nurisso, Eva-Laure Matera, Anne Tourette, Romain Haudecoeur, Doriane Mathe, Marine Peuchmaur, Grégory Bouchaud, Basile Pérès, Antoine Magnan, Ahcène Boumendjel, Guillaume Monneret, Justine Esmenjaud, Eve Mattei, Cédric Boyère, Université de Lyon (COMUE), Institut National de la Santé et de la Recherche Médicale (INSERM), Dynamique des Structures et Interactions des Macromolécules Biologiques - Pôle de La Réunion (DSIMB Réunion), Biologie Intégrée du Globule Rouge (BIGR (UMR_S_1134 / U1134)), Institut National de la Transfusion Sanguine [Paris] (INTS)-Université Paris Diderot - Paris 7 (UPD7)-Université de La Réunion (UR)-Université des Antilles (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Transfusion Sanguine [Paris] (INTS)-Université Paris Diderot - Paris 7 (UPD7)-Université de La Réunion (UR)-Université des Antilles (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Grenoble Alpes (COMUE) (UGA), School of Pharmaceutical Sciences, Nanjing Tech University, Unité de recherche sur les Biopolymères, Interactions Assemblages (BIA), Institut National de la Recherche Agronomique (INRA), Institut du thorax, Université de Nantes (UN)-IFR26-Institut National de la Santé et de la Recherche Médicale (INSERM), Hospices Civils de Lyon (HCL), Labex ARCANE, and CBH-EUR-GS [ANR-17-EURE-0003]
Subjects: 0301 basic medicine, Gene isoform, Models, Molecular, Chalcone, Drug Evaluation, Preclinical, Pharmacology, Basophil degranulation, Cell Degranulation, Dermatitis, Atopic, 03 medical and health sciences, chemistry.chemical_compound, Route of administration, Mice, Phosphatidylinositol 3-Kinases, Chalcones, Piperidines, Drug Discovery, [SDV.IDA]Life Sciences [q-bio]/Food engineering, medicine, Animals, Humans, [SPI.GPROC]Engineering Sciences [physics]/Chemical and Process Engineering, Allergic properties, Protein Kinase Inhibitors, PI3K delta, Phosphoinositide-3 Kinase Inhibitors, chemistry.chemical_classification, Chemistry, Organic Chemistry, Degranulation, General Medicine, Atopic dermatitis, medicine.disease, Asthma, 3. Good health, Basophils, Disease Models, Animal, 030104 developmental biology, Enzyme, Anti-atopic activity, Toxicity
Abstract: International audience; Phosphatidylinositide 3-kinases (PI3Ks) are widely expressed enzymes involved in membrane signalization pathways. Attempts to administer inhibitors with broad activity against different isoforms have failed due to toxicity. Conversely the PI3K delta isoform is much more selectively expressed, enabling therapeutic targeting of this isoform. Of particular interest PI3K delta is expressed in human basophils and its inhibition has been shown to reduce anti-IgE induced basophil degranulation, suggesting that PI3K delta inhibitors could be useful as anti-allergy drugs. Herein, we report for the first time the activity of compounds derived from chalcone scaffolds as inhibitors of normal human basophil degranulation and identified the most active compound with anti-PI3K delta properties that was investigated in preclinical models. Compound 18, namely 1-[2-hydroxy-4,6-dimethoxy-3-(N-methylpiperidin-4-yl)pheny1]-3(2,4,6-trimethoxypheny1)-prop-2-en-1-one, was found to inhibit normal human basophil degranulation in a dose-dependent manner. In a murine model of ovalbumin-induced asthma, compound 18 was shown to reduce expiratory pressure while its impact on the inflammatory infiltrate in alveolar lavage and total lung was dependent on the route of administration. In a DNFB-induced model of atopic dermatitis compound 18 administered systemically proved to be as potent as topical betamethasone. These results support the anti-atopic and allergic properties of the title compound and warrant further clinical development. (C) 2018 Elsevier Masson SAS
Published: 2018
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12. Glycosyl-Substituted Dicarboxylates as Detergents for the Extraction, Overstabilization, and Crystallization of Membrane Proteins

Author: Sandrine Magnard, Pierre Falson, Saravanan Mounien, Sébastien Igonet, Veronica Zampieri, Romain Haudecoeur, Cédric Boyère, Marine Peuchmaur, Kim-Anh Nguyen, Anass Jawhari, Vincent Chaptal, Ahcène Boumendjel, Ikram Benammar, Laboratoire de Recherche Vasculaire Translationnelle (LVTS (UMR_S_1148 / U1148)), Université Paris Diderot - Paris 7 (UPD7)-Université Paris 13 (UP13)-Institut National de la Santé et de la Recherche Médicale (INSERM), Département de pharmacochimie moléculaire (DPM ), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Microbiologie moléculaire et biochimie structurale / Molecular Microbiology and Structural Biochemistry (MMSB), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Institut de biologie et chimie des protéines [Lyon] (IBCP), and CALIXAR
Subjects: 0301 basic medicine, Glycosylation, ATPase, Detergents, Carboxylic Acids, Crystallography, X-Ray, 010402 general chemistry, 01 natural sciences, Catalysis, law.invention, chemistry.chemical_compound, 03 medical and health sciences, law, Amphiphile, Glycosyl, Crystallization, [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM], ComputingMilieux_MISCELLANEOUS, Adenosine Triphosphatases, biology, [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM], Protein Stability, Hydrogen bond, [CHIM.ORGA]Chemical Sciences/Organic chemistry, Receptors, Purinergic P1, Membrane Proteins, Hydrogen Bonding, General Chemistry, General Medicine, Combinatorial chemistry, 0104 chemical sciences, Membrane, 030104 developmental biology, Membrane protein, Structural biology, chemistry, biology.protein, ATP-Binding Cassette Transporters
Abstract: To tackle the problems associated with membrane protein (MP) instability in detergent solutions, we designed a series of glycosyl-substituted dicarboxylate detergents (DCODs) in which we optimized the polar head to clamp the membrane domain by including, on one side, two carboxyl groups that form salt bridges with basic residues abundant at the membrane-cytoplasm interface of MPs and, on the other side, a sugar to form hydrogen bonds. Upon extraction, the DCODs 8 b, 8 c, and 9 b preserved the ATPase function of BmrA, an ATP-binding cassette pump, much more efficiently than reference or recently designed detergents. The DCODs 8 a, 8 b, 8 f, 9 a, and 9 b induced thermal shifts of 20 to 29 °C for BmrA and of 13 to 21 °C for the native version of the G-protein-coupled adenosine receptor A2A R. Compounds 8 f and 8 g improved the diffraction resolution of BmrA crystals from 6 to 4 A. DCODs are therefore considered to be promising and powerful tools for the structural biology of MPs.
Published: 2018
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13. Traditional uses, phytochemistry and pharmacological properties of African Nauclea species: A review

Author: Basile Pérès, Germain Sotoing Taiwe, Benjamin Boucherle, Maxime Rome, Romain Haudecoeur, Marine Peuchmaur, and Ahcène Boumendjel
Subjects: Pharmacology, Nauclea, Phytochemistry, Plants, Medicinal, biology, Traditional medicine, 010405 organic chemistry, Phytochemicals, Rubiaceae, biology.organism_classification, 01 natural sciences, 0104 chemical sciences, 010404 medicinal & biomolecular chemistry, Phytochemical, Genus, Ethnobotany, Drug Discovery, Threatened species, Animals, Humans, Medicinal plants, Ethnomedicine, Medicine, African Traditional, Phytotherapy
Abstract: Ethnopharmacoalogical relevance The genus Nauclea in Africa comprises seven species. Among them, N. latifolia , N. diderrichii and N. pobeguinii are widely used by the local population in traditional remedies. Preparation from various parts of plants (e.g. roots, bark, leaves) are indicated by traditional healers for a wide range of diseases including malaria, pain, digestive ailments or metabolic diseases. Materials and methods A literature search was conducted on African species of the genus Nauclea using scientific databases such as Google Scholar, Pubmed or SciFinder. Every document of ethnopharmacological, phytochemical or pharmacological relevance and written in English or French were analyzed. Results and discussion The Nauclea genus is used as ethnomedicine all along sub-Saharan Africa. Several local populations consider Nauclea species as a major source of remedies for malaria. In this regard, two improved traditional medicines are currently under development using extracts from N. latifolia and N. pobeguinii . Concerning the chemical composition of the Nauclea genus, indoloquinolizidines alkaloids could be considered as the major class of compounds as they are reported in every analyzed Nauclea species, with numerous structures identified. Based on traditional indications a considerable amount of pharmacological studies were conducted to ensure activity and attempt to link them to the presence of particular compounds in plant extracts. Conclusion Many experimental studies using plant extracts of the African species of the genus Nauclea validate traditional indications (e.g. malaria and pain). However, bioactive compounds are rarely identified and therefore, there is a clear need for further evaluations as well as for toxicity experiments. The sustainability of these plants, especially of N. diderrichii , a threatened species, should be kept in mind to adapt local uses and preparation modes of traditional remedies.
Published: 2017

14. 2-Hydroxypyridine-N-oxide-Embedded Aurones as Potent Human Tyrosinase Inhibitors

Author: Romain Haudecoeur, Elisabetta Bergantino, Catherine Belle, Marcello Carotti, Renaud Hardré, Elina Buitrago, Aurélie Gouron, Ahcène Boumendjel, Luigi Bubacco, Marius Réglier, Marc Maresca, Hélène Jamet, Département de pharmacochimie moléculaire (DPM ), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Institut National de l'Environnement Industriel et des Risques (INERIS), Institut des Sciences Moléculaires de Marseille (ISM2), Aix Marseille Université (AMU)-École Centrale de Marseille (ECM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Università degli Studi di Padova = University of Padua (Unipd), Département de Chimie Moléculaire - Chimie Inorganique Redox (DCM - CIRE ), Département de Chimie Moléculaire (DCM), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Department of Biology, Department of Biology, University of Padova, Universita degli Studi di Padova, Département de Chimie Moléculaire - Chimie Inorganique Redox Biomimétique (DCM - CIRE ), and Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS)-École Centrale de Marseille (ECM)-Institut de Chimie du CNRS (INC)
Subjects: 0301 basic medicine, Cell lysates, Stereochemistry, Tyrosinase, Human tyrosinase, 01 natural sciences, Biochemistry, 03 medical and health sciences, chemistry.chemical_compound, aurones, [CHIM.ANAL]Chemical Sciences/Analytical chemistry, Drug Discovery, Aurone, Moiety, QM/MM calculations, human melanoma, transition state analogues, 2-hydroxypyridine-N-oxide, ComputingMilieux_MISCELLANEOUS, Low toxicity, 010405 organic chemistry, Chemistry, Organic Chemistry, In vitro, 3. Good health, 0104 chemical sciences, 030104 developmental biology, Human melanoma
Abstract: With the aim to develop effective and selective human tyrosinase inhibitors, we investigated aurone derivatives whose B-ring was replaced by a non-oxidizable 2-hydroxypyridine-N-oxide (HOPNO) moiety. These aurones were synthesized and evaluated as inhibitors of purified human tyrosinase. Excellent inhibition activity was revealed and rationalized by theoretical calculations. The aurone backbone was especially found to play a crucial role, as the HOPNO moiety alone provided very modest activity on human tyrosinase. Furthermore, the in vitro activity was confirmed by measuring the melanogenesis suppression ability of the compounds in melanoma cell lysates and whole cells. Our study reveals that HOPNO-embedded 6-hydroxyaurone is to date the most effective inhibitor of isolated human tyrosinase. Owing to its low toxicity and its high inhibition activity, it could represent a milestone on the path toward new valuable agents in dermocosmetics, as well as in medical fields where it was recently suggested that ty...
Published: 2017
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15. 2-Hydroxypyridine

Author: Romain, Haudecoeur, Marcello, Carotti, Aurélie, Gouron, Marc, Maresca, Elina, Buitrago, Renaud, Hardré, Elisabetta, Bergantino, Hélène, Jamet, Catherine, Belle, Marius, Réglier, Luigi, Bubacco, and Ahcène, Boumendjel
Abstract: With the aim to develop effective and selective human tyrosinase inhibitors, we investigated aurone derivatives whose B-ring was replaced by a non-oxidizable 2-hydroxypyridine
Published: 2016

16. Are Human Tyrosinase and Related Proteins Suitable Targets for Melanoma Therapy?

Author: Elina Buitrago, Ahcène Boumendjel, Renaud Hardré, Marius Réglier, Catherine Belle, Hélène Jamet, Romain Haudecoeur, Luigi Bubacco, Institut des Sciences Moléculaires de Marseille (ISM2), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS)-École Centrale de Marseille (ECM)-Institut de Chimie du CNRS (INC), Département de pharmacochimie moléculaire (DPM ), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Département de Chimie Moléculaire - Chimie Inorganique Redox Biomimétique (DCM - CIRE ), Département de Chimie Moléculaire (DCM), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Département de Chimie Moléculaire - Chimie Théorique (DCM - CT), Department of Biology, Universita degli Studi di Padova, Aix Marseille Université (AMU)-École Centrale de Marseille (ECM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Département de Chimie Moléculaire - Chimie Inorganique Redox (DCM - CIRE ), and Università degli Studi di Padova = University of Padua (Unipd)
Subjects: Models, Molecular, Tyrosinase, Biology, 010402 general chemistry, 01 natural sciences, Melanoma, TRP-1, TRP-2, Tyrosinase effectors, Drug Discovery3003 Pharmaceutical Science, Melanin, In vivo, [CHIM.ANAL]Chemical Sciences/Analytical chemistry, Drug Discovery, medicine, Humans, Amino Acid Sequence, Tyrosine, Peptide sequence, ComputingMilieux_MISCELLANEOUS, chemistry.chemical_classification, Sequence Homology, Amino Acid, integumentary system, Monophenol Monooxygenase, 010405 organic chemistry, General Medicine, Monooxygenase, medicine.disease, Neoplasm Proteins, 3. Good health, 0104 chemical sciences, Enzyme, Biochemistry, chemistry, Biocatalysis, sense organs
Abstract: Among the human copper-containing monooxygenases, Tyrosinase (Ty) is an important enzyme involved in the determinant step of the biosynthetic pathway of melanin pigment. In this pathway, Ty catalyzes the tyrosine monooxygenation into L-DOPA-quinone, which is the precursor of the skin pigment melanin. Ty inhibitors/activators are a well-established approach for controlling in vivo melanin production, so their development has a huge economical and industrial impact. Moreover, recent publications highlight that targeting tyrosinase with inhibitors/activators to treat melanogenesis disorders is one of many possible approaches, due to the complex biochemical reaction involved in the melanin synthesis.
Published: 2016
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17. Nauclea latifolia: biological activity and alkaloid phytochemistry of a West African tree

Author: Emerson Ferreira Queiroz, Michel De Waard, Romain Haudecoeur, Jean-Luc Wolfender, Benjamin Boucherle, Ahcène Boumendjel, Richard J. Robins, Institut de Chimie de Clermont-Ferrand (ICCF), Université Blaise Pascal - Clermont-Ferrand 2 (UBP)-SIGMA Clermont (SIGMA Clermont)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Département de pharmacochimie moléculaire (DPM ), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), unité de recherche de l'institut du thorax UMR1087 UMR6291 (ITX), Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Ecole de Pharmacie Genève Lausanne (EPGL), Chimie Et Interdisciplinarité : Synthèse, Analyse, Modélisation (CEISAM), Université de Nantes - UFR des Sciences et des Techniques (UN UFR ST), Université de Nantes (UN)-Université de Nantes (UN)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC), Université de Nantes (UN), Unité de recherche de l'institut du thorax (ITX-lab), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), and Université de Nantes (UN)-Université de Nantes (UN)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Nauclea, Phytochemistry, Rubiaceae, Biology, 01 natural sciences, Biochemistry, Plant Roots, Indole Alkaloids, Trees, Drug Discovery, Botany, Malaria/drug therapy, Trees/chemistry, Animals, [CHIM]Chemical Sciences, Tramadol, ddc:615, Analgesics, Opioid/therapeutic use, Plant Roots/chemistry, Indole Alkaloids/chemistry/isolation & purification/pharmacology, Molecular Structure, 010405 organic chemistry, Alkaloid, Organic Chemistry, Biological activity, biology.organism_classification, 3. Good health, 0104 chemical sciences, Malaria, Sarcocephalus latifolius, Analgesics, Opioid, 010404 medicinal & biomolecular chemistry, West african, Phytochemical, Tramadol/chemistry/isolation & purification/metabolism/pharmacology, Rubiaceae/chemistry, Medicine, Traditional
Abstract: Covering up to 2016, Nauclea latifolia (syn. Sarcocephalus latifolius, Rubiaceae), commonly called the African pincushion tree, is a plant widely used in folk medicine in different regions of Africa for treating a variety of illnesses, including malaria, epilepsy and pain. N. latifolia has not only drawn the interest of traditional healers but also of phytochemists, who have identified a range of bioactive indole alkaloids in its tissue. More recently, following up on the traditional use of extracts in pain management, a bio-guided purification from the roots of the tree led to the identification of the active ingredient as tramadol, available as a synthetic analgesic since the 1970s. The discovery of this compound as a natural phytochemical was highlighted worldwide. This review focuses on the correlation between extracted compounds and pharmacological activities, paying special attention to infectious diseases and neurologically-related disorders. A critical analysis of the data reported so far on the natural origin of tramadol and its proposed biosynthesis is also presented.
Published: 2016
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18. Structure-Activity Relationships in the Development of Allosteric Hepatitis C Virus RNA-Dependent RNA Polymerase Inhibitors: Ten Years of Research

Author: Romain Haudecoeur, Marine Peuchmaur, Jean-Michel Pawlotsky, Abdelhakim Ahmed-Belkacem, and Ahcène Boumendjel
Subjects: Pharmacology, Liver infection, viruses, Hepatitis C virus, RNA, Hepatitis C, Biology, medicine.disease, medicine.disease_cause, Virology, chemistry.chemical_compound, chemistry, Hepatocellular carcinoma, RNA polymerase, Drug Discovery, medicine, biology.protein, Molecular Medicine, NS5B, Polymerase
Abstract: Hepatitis C is a viral liver infection considered as the major cause of cirrhosis and hepatocellular carcinoma (HCC). Hepatitis C virus (HCV) possesses a single positive strand RNA genome encoding a polyprotein composed of approximatively 3000 amino acids. The polyprotein is cleaved at multiple sites by cellular and viral proteases to liberate structural and nonstructural (NS) proteins. NS5B, the RNA-dependent RNA polymerase (RdRp), which catalyzes the HCV RNA replication has emerged as an attractive target for the development of specifically targeted antiviral therapy for HCV (DAA, for direct-acting antivirals). In the last 10 years, a growing number of non-nucleoside compounds have been reported as RdRp inhibitors and few are undergoing clinical trials. Over the past 5 years, several reviews were published all describing potentially active molecules. To the best of our knowledge, only one review covers the structure-activity relationships.(1) In this review, we will discuss the reported non-nucleoside molecules acting as RdRp inhibitors according to their chemical class especially focusing on structure-activity relationship aspects among each class of compounds. Thereafter, we will attempt to address the global structural requirements needed for the design of specific inhibitors of RdRp.
Published: 2012
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19. Recent Advances in the Medicinal Chemistry of Aurones

Author: Romain Haudecoeur and Ahcène Boumendjel
Subjects: Flavonoids, Pharmacology, Molecular Structure, business.industry, Organic Chemistry, Biochemistry, Medicinal chemistry, Structure-Activity Relationship, Drug Discovery, Animals, Humans, Molecular Medicine, Medicine, business, Benzofurans
Abstract: The first review regarding the potential of aurones as promising drug candidates was reported in 2003. Since, considerable efforts have been made to explore the pharmacological and therapeutical activities of aurones. In this regard, many biological areas were concerned, including major pathological, such as cancer and neurodegenerative disorders. The aim of the present report is to highlight the progress made during the last ten years on the medicinal chemistry of aurones. A special focus will be made on the structure-activity relationship aspects among aurones and especially in case where aurones were found highly active than the corresponding flavones and chalcones.
Published: 2012
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20. Refinement of arylthiosemicarbazone pharmacophore in inhibition of mushroom tyrosinase

Author: Carole Dubois, Catherine Belle, Romain Haudecoeur, Samir Yahiaoui, Wei Yi, Huacan Song, Marius Réglier, Ahcène Boumendjel, Renaud Hardré, Département de pharmacochimie moléculaire (DPM), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF), Institut des Sciences Moléculaires de Marseille (ISM2), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS)-École Centrale de Marseille (ECM)-Institut de Chimie du CNRS (INC), Physique et mécanique des milieux hétérogenes (UMR 7636) (PMMH), Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Département de Chimie Moléculaire - Chimie Inorganique Redox Biomimétique (DCM - CIRE), Département de Chimie Moléculaire (DCM), Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université Joseph Fourier - Grenoble 1 (UJF)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université Joseph Fourier - Grenoble 1 (UJF), Université Joseph Fourier - Grenoble 1 (UJF)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Aix Marseille Université (AMU)-École Centrale de Marseille (ECM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Département de Chimie Moléculaire - Chimie Inorganique Redox (DCM - CIRE), and Université Joseph Fourier - Grenoble 1 (UJF)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Thiosemicarbazones, Spectrometry, Mass, Electrospray Ionization, Magnetic Resonance Spectroscopy, Tyrosinase, Skin Pigmentation, 010402 general chemistry, 01 natural sciences, Melanin, Inhibitory Concentration 50, chemistry.chemical_compound, Biosynthesis, Drug Discovery, [CHIM]Chemical Sciences, Humans, Enzyme Inhibitors, Tyrosine, ComputingMilieux_MISCELLANEOUS, Melanins, Pharmacology, chemistry.chemical_classification, Monophenol Monooxygenase, 010405 organic chemistry, Organic Chemistry, Biological activity, General Medicine, 0104 chemical sciences, 3. Good health, Enzyme, Biochemistry, chemistry, Pharmacophore, Agaricales, Kojic acid
Abstract: Melanin play a major role in human skin protection and their biosynthesis is vital. Due to their color, they contribute to the skin pigmentation. Tyrosinase is a key enzyme involved in the first stage of melanin biosynthesis, it catalyzes the transformation of tyrosine into l-dopaquinone. The aim of the present study was to study molecules able to inhibit tyrosinase to be used in treating depigmentation-related disorders. In this study, we targeted arylthiosemicarbazone analogs with the aim to contribute to the identification of the optimal aryl ring to be linked to the thiosemicarbazone moiety. The biological activity was evaluated on commercial mushroom tyrosinase which was purified prior use. The results demonstrated that several of our compounds (1a-h, 1j, 1r and 5) had more potent inhibitory activities than kojic acid which was used as the reference inhibitor.
Published: 2011
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21. Synthetic G-Quartets as Versatile Nanotools for the Luminescent Detection of G-Quadruplexes

Author: Fares Katranji, Marc Pirrotta, Loic Stefan, David Monchaud, Marine Levillain, Aurélien Laguerre, Romain Haudecoeur, Institut de Chimie Moléculaire de l'Université de Bourgogne [Dijon] (ICMUB), Université de Bourgogne (UB)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Département de pharmacochimie moléculaire (DPM), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF), Conception, synthèse et vectorisation de biomolécules. (CSVB), Université Paris Descartes - Paris 5 (UPD5)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut Curie [Paris], Université de Bourgogne (UB)-Centre National de la Recherche Scientifique (CNRS), Université Grenoble Alpes (UGA)-Université Joseph Fourier - Grenoble 1 (UJF)-Centre National de la Recherche Scientifique (CNRS), and Institut Curie-Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)
Subjects: Models, Molecular, Luminescence, Guanine, Supramolecular chemistry, Nanotechnology, G-quadruplex, Tasq, Nucleobase, chemistry.chemical_compound, Dota, Organometallic Compounds, Nanobiotechnology, [CHIM]Chemical Sciences, Luminescent Agents, Terbium, QD1-999, ComputingMilieux_MISCELLANEOUS, Molecular switch, Chemistry, Pyrene, General Medicine, General Chemistry, Thymine, G-Quadruplexes, Drug Design, Luminescent Measurements, Graphite
Abstract: Recent years have witnessed a tremendous increase in the biotechnological applications of nucleic acid-based nanotools. Beyond their biological relevance, nucleobases have indeed found new scopes of applications in bionanotechnology, which are expanding nowadays at an accelerated pace. Among the four canonical nucleobases (adenine, guanine, cytosine and thymine), guanine is certainly the most useful and used base, thanks to its versatile H-bond donating/accepting properties that make it suitable for being involved in various assemblies ranging from base-pairs to base-quartets. Here, we would like to report on an innovative guanine-based molecular tool named Tb. Pyro-DOTASQ: this metal complex has a sophisticated chemical structure that allows formation of an intramolecular G-quartet upon interaction with alternative secondary structures known as G-quadruplexes. This target-promoted molecular switch triggers a luminescence response that would permit the use of Tb. Pyro-DOTASQ to search and detect quadruplex-forming DNA and RNA sequences: its unique design indeed allows it i) to create specific interaction with quadruplexes, ii) to provide an easily readable luminescent output to monitor this association and iii) to be readily immobilized on graphene surface, thus making Tb. Pyro-DOTASQ a high-value molecular device. Results obtained in the course of in-depth biophysical analyses raise questions about the actual supramolecular structure of Tb. Pyro-DOTASQ: these results thus shed a bright light on the care that must be exercised when using intricate molecular architectures to construct elaborated supramolecular metal complexes.
Published: 2015
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22. Biomimetic synthesis of Tramadol

Author: Marcos Marçal Ferreira Queiroz, Germain Sotoing Taiwe, Romain Haudecoeur, Thierry Lomberget, Jean-Luc Wolfender, Marc Le Borgne, Soura Challal, Laurence Marcourt, Ahcène Boumendjel, Florine Lecerf-Schmidt, Basile Pérès, Richard J. Robins, Emerson Ferreira Queiroz, Michel De Waard, Département de Chimie Moléculaire - Chimie Inorganique Redox Biomimétique (DCM - CIRE), Département de Chimie Moléculaire (DCM), Université Joseph Fourier - Grenoble 1 (UJF)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), School of Pharmaceutical Sciences, Université de Lausanne (UNIL)-University of Geneva [Switzerland], INSERM U836, équipe 3, Canaux calciques, fonctions et pathologies, Grenoble Institut des Neurosciences (GIN), Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Department of Zoology and Animal Physiology, Faculty of Science-University of Buea-Faculty of Science-University of Buea-Department of Animal Biology and Physiology [university of Yaoundé], University of Yaoundé [Cameroun]-University of Yaoundé [Cameroun], Méthodologie de synthèse et molécules bioactives (MSMB), Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, Biomolécules Cancer et Chimiorésistances (B2C), Université Claude Bernard Lyon 1 (UCBL), School Pharmaceutical Sciences, Phytochemistry and Bioactive Natural Products, Université de Lausanne, Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM), Chimie Et Interdisciplinarité : Synthèse, Analyse, Modélisation (CEISAM), Université de Nantes - UFR des Sciences et des Techniques (UN UFR ST), Université de Nantes (UN)-Université de Nantes (UN)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC), Département de pharmacochimie moléculaire (DPM), and Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF)
Subjects: Nauclea, Magnetic Resonance Spectroscopy, Stereochemistry, [CHIM.THER]Chemical Sciences/Medicinal Chemistry, Catalysis, Mass Spectrometry, [SDV.SP.MED]Life Sciences [q-bio]/Pharmaceutical sciences/Medication, In vivo, Biomimetics, Biomimetic synthesis, Tramadol/chemical synthesis, Materials Chemistry, medicine, ComputingMilieux_MISCELLANEOUS, Tramadol, Chromatography, High Pressure Liquid, ddc:615, biology, Chemistry, Metals and Alloys, General Chemistry, [SDV.BV.BOT]Life Sciences [q-bio]/Vegetal Biology/Botanics, [SDV.SP]Life Sciences [q-bio]/Pharmaceutical sciences, biology.organism_classification, Surfaces, Coatings and Films, Electronic, Optical and Magnetic Materials, Analgesics, Opioid, Ceramics and Composites, Opioid analgesics, Analgesics, Opioid/chemical synthesis, medicine.drug
Abstract: Tramadol has recently been isolated from the roots and bark of Nauclea latifolia. A plausible biosynthetic pathway has been proposed and the product-precursor relationship has been probed by (13)C position-specific isotope analysis. By further exploring this pathway, we demonstrate that a key step of the proposed pathway can be achieved using mild conditions that mimic in vivo catalysis.
Published: 2015
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23. Investigation of Binding-Site Homology between Mushroom and Bacterial Tyrosinases by Using Aurones as Effectors

Author: Renaud Hardré, Luigi Bubacco, Catherine Belle, Ahcène Boumendjel, Anne Milet, Aurélie Gouron, Romain Haudecoeur, Mark Lightbody, Marius Réglier, Hélène Jamet, Carole Dubois, Elisabetta Bergantino, Département de pharmacochimie moléculaire (DPM), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF), Institut National de l'Environnement Industriel et des Risques (INERIS), Institut des Sciences Moléculaires de Marseille (ISM2), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS)-École Centrale de Marseille (ECM)-Institut de Chimie du CNRS (INC), Département de Chimie Moléculaire - Chimie Théorique (DCM - CT), Département de Chimie Moléculaire (DCM), Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université Joseph Fourier - Grenoble 1 (UJF)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université Joseph Fourier - Grenoble 1 (UJF), Department of Biology, University of Padova, Universita degli Studi di Padova, Department of Biology, Département de Chimie Moléculaire - Chimie Inorganique Redox Biomimétique (DCM - CIRE), Université Joseph Fourier - Grenoble 1 (UJF)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Aix Marseille Université (AMU)-École Centrale de Marseille (ECM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Université Joseph Fourier - Grenoble 1 (UJF)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Università degli Studi di Padova = University of Padua (Unipd), and Département de Chimie Moléculaire - Chimie Inorganique Redox (DCM - CIRE)
Subjects: Models, Molecular, Stereochemistry, Tyrosinase, Agaricus, Context (language use), Biology, 010402 general chemistry, 01 natural sciences, Biochemistry, Hydroxylation, chemistry.chemical_compound, Structure-Activity Relationship, Biosynthesis, Aurone, [CHIM]Chemical Sciences, Binding site, Enzyme Inhibitors, Molecular Biology, ComputingMilieux_MISCELLANEOUS, Benzofurans, chemistry.chemical_classification, Binding Sites, Dose-Response Relationship, Drug, Molecular Structure, 010405 organic chemistry, Effector, Monophenol Monooxygenase, Organic Chemistry, Streptomyces antibioticus, 0104 chemical sciences, Enzyme, chemistry, Molecular Medicine
Abstract: Tyrosinase is a copper-containing enzyme found in plants and bacteria, as well as in humans, where it is involved in the biosynthesis of melanin-type pigments. Tyrosinase inhibitors have attracted remarkable research interest as whitening agents in cosmetology, antibrowning agents in food chemistry, and as therapeutics. In this context, commercially available tyrosinase from mushroom (TyM) is frequently used for the identification of inhibitors. This and bacterial tyrosinase (TyB) have been the subjects of intense biochemical and structural studies, including X-ray diffraction analysis, and this has led to the identification of structural homology and divergence among enzymes from different sources. To better understand the behavior of potential inhibitors of TyM and TyB, we selected the aurone family-previously identified as potential inhibitors of melanin biosynthesis in human melanocytes. In this study, a series of 24 aurones with different hydroxylation patterns at the A- and B-rings were evaluated on TyM and TyB. The results show that, depending on the hydroxylation pattern of A- and B-rings, aurones can behave as inhibitors, substrates, and activators of both enzymes. Computational analysis was performed to identify residues surrounding the aurones in the active sites of both enzymes and to rationalize the interactions. Our results highlight similarities and divergence in the behavior of TyM and TyB toward the same set of molecules.
Published: 2014
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24. B-ring modified aurones as promising allosteric inhibitors of hepatitis C virus RNA-dependent RNA polymerase

Author: Ahcène Boumendjel, Marine Peuchmaur, Amel Meguellati, Romain Haudecoeur, Jean-Michel Pawlotsky, Abdelhakim Ahmed-Belkacem, Wei Yi, Rozenn Brillet, Marie Crouillère, Département de pharmacochimie moléculaire (DPM), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Molecular virology and immunology – Physiopathology and therapeutic of chronic viral hepatitis (Team 18) (Inserm U955), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Hôpital Henri Mondor, FRM, ANRS, ANR-11-LABX-0003,ARCANE,Grenoble, une chimie bio-motivée(2011), Peuchmaur, Marine, and Grenoble, une chimie bio-motivée - - ARCANE2011 - ANR-11-LABX-0003 - LABX - VALID
Subjects: Models, Molecular, Hepatitis C Virus, Protein Conformation, Hepatitis C virus, [SDV]Life Sciences [q-bio], Allosteric regulation, RNA-dependent RNA polymerase, Hepacivirus, medicine.disease_cause, Antiviral Agents, chemistry.chemical_compound, Allosteric Regulation, RNA polymerase, Drug Discovery, Aurone, [CHIM] Chemical Sciences, medicine, Moiety, [CHIM]Chemical Sciences, Enzyme Inhibitors, Polymerase, Benzofurans, Pharmacology, biology, Chemistry, Organic Chemistry, General Medicine, Aurones, [SDV] Life Sciences [q-bio], Biochemistry, Docking (molecular), biology.protein
Abstract: International audience; Following our recent report showing the potential of naturally occurring aurones (2benzylidenebenzofuran-3(2H)-ones) as anti-hepatitis C virus (HCV) agents, efforts were continued in order to refine the structural requirements for the inhibitory effect on HCV RNA-dependent RNA polymerase (RdRp). In this study, we targeted the Bring moiety of aurones with the aim to improve structural features associated with higher inhibition of the targeted polymerase. In vitro evaluation of the RdRp inhibitory activity of the 37 newly synthesized compounds pointed out that the replacement of the Bring with a N-substituted indole moiety induced the highest inhibitory effect. Of these, compounds 31, 40 and 41 were found to be the most active (IC50 = 2.3-2.4 µM). Docking experiments performed with the most active compounds revealed that the allosteric thumb pocket I of RdRp is the binding pocket for aurone analogues.
Published: 2014
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25. Multitasking Water-Soluble Synthetic G-Quartets: From Preferential RNA-Quadruplex Interaction to Biocatalytic Activity

Author: David Monchaud, Loic Stefan, Romain Haudecoeur, Département de pharmacochimie moléculaire (DPM), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF), Institut de Chimie Moléculaire de l'Université de Bourgogne [Dijon] (ICMUB), Université de Bourgogne (UB)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Conception, synthèse et vectorisation de biomolécules. (CSVB), Université Paris Descartes - Paris 5 (UPD5)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut Curie [Paris], Université Grenoble Alpes (UGA)-Université Joseph Fourier - Grenoble 1 (UJF)-Centre National de la Recherche Scientifique (CNRS), Université de Bourgogne (UB)-Centre National de la Recherche Scientifique (CNRS), and Institut Curie-Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)
Subjects: Stereochemistry, Guanine, Supramolecular chemistry, Deoxyribozyme, 010402 general chemistry, G-Quartets, G-quadruplex, 01 natural sciences, Catalysis, chemistry.chemical_compound, [CHIM]Chemical Sciences, ComputingMilieux_MISCELLANEOUS, 010405 organic chemistry, Organic Chemistry, Water, RNA, DNA, General Chemistry, 0104 chemical sciences, G-Quadruplexes, chemistry, Intramolecular force, Biocatalysis, Hemin, Oxidation-Reduction
Abstract: Natural G-quartets, a cyclic and coplanar array of four guanine res- idues held together through a Watson- Crick/Hoogsteen hydrogen-bond net- work, have received recently much at- tention due to their involvement in G- quadruplex DNA, an alternative higher-order DNA structure strongly suspected to play important roles in key cellular events. Besides this, syn- thetic G-quartets (SQ), which artificial- ly mimic native G-quartets, have also been widely studied for their involve- ment in nanotechnological applications (i.e., nanowires, artificial ion channels, etc.). In contrast, intramolecular syn- thetic G-quartets (iSQ), also named template-assembled synthetic G-quar- tets (TASQ), have been more sparingly investigated, despite a technological potential just as interesting. Herein, we report on a particular iSQ named PNA DOTASQ, which demonstrates very interesting properties in terms of DNA and RNA interaction (notably its selec- tive recognition of quadruplexes ac- cording to a bioinspired process) and catalytic activities, through its ability to perform peroxidase-like hemin-mediat- ed oxidations either in an autonomous fashion (i.e., as pre-catalyst for TASQ- zyme reactions) or in conjunction with quadruplex DNA (i.e., as enhancing agents for DNAzyme processes). These results provide a solid scientific basis for TASQ to be used as multitasking tools for bionanotechnological applica- tions.
Published: 2013
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26. Occurrence of the Synthetic Analgesic Tramadol in an African Medicinal Plant

Author: Bruno Bonaz, Chantal Beney, Ahcène Boumendjel, Romain Haudecoeur, Antoine Depaulis, Florence Souard, Marc Le Borgne, Tanguy Chabrol, Michel De Waard, Richard J. Robins, Elisabeth Ngo Bum, Soura Challal, Thierry Lomberget, Catherine Lavaud, Laurence Marcourt, Germain Sotoing Taiwe, Jean-Luc Wolfender, Emerson Ferreira Queiroz, Valérie Sinniger, Canepari, Marco, Département de pharmacochimie moléculaire (DPM), Université Joseph Fourier - Grenoble 1 (UJF)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), INSERM U836, équipe 3, Canaux calciques, fonctions et pathologies, Grenoble Institut des Neurosciences (GIN), Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Department of Zoology and Animal Physiology, University of Buea-University of Buea-Department of Animal Biology and Physiology, University of Yaoundé [Cameroun]-Faculty of Science-University of Yaoundé [Cameroun]-Faculty of Science, Département des Sciences Biologiques [Univ Ngaoundéré] (UN-FS), Faculté de Sciences [Univ Ngaoundéré] (UN-FS), Université de Ngaoundéré/University of Ngaoundéré [Cameroun] (UN)-Université de Ngaoundéré/University of Ngaoundéré [Cameroun] (UN), INSERM U836, équipe 9, Dynamique des réseaux synchrones épileptiques, Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM), INSERM U836, équipe 8, Stress et interactions neurodigestives, School of Pharmaceutical Sciences, Université de Lausanne = University of Lausanne (UNIL)-Université de Genève = University of Geneva (UNIGE), Biomolécules Cancer et Chimiorésistances (B2C), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, Fonctions Normales et Pathologiques de la Barrière Cutanée [Hôpital Edouard Herriot - HCL], Université de Lyon-Université de Lyon-Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Laboratoire de Pharmacognosie, Université de Reims Champagne-Ardenne (URCA), Chimie Et Interdisciplinarité : Synthèse, Analyse, Modélisation (CEISAM), Université de Nantes - UFR des Sciences et des Techniques (UN UFR ST), Université de Nantes (UN)-Université de Nantes (UN)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Inserm, LabEx Ion Channels, ISPB of Lyon, Agence Française pour la Francophonie, Labex ARCANE, Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF), Université de Lausanne (UNIL)-University of Geneva [Switzerland], and Université de Nantes (UN)-Université de Nantes (UN)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)
Subjects: Moderate to severe, Analgesic effect, Phytochemicals, Analgesic, Pain relief, Pain, Pharmacology, 010402 general chemistry, 01 natural sciences, Catalysis, medicine, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Medicinal plants, Tramadol, Plants, Medicinal, Plant Extracts, business.industry, 010405 organic chemistry, General Chemistry, General Medicine, Opioid chemistry, 3. Good health, 0104 chemical sciences, Analgesics, Opioid, Morphine, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], business, medicine.drug
Abstract: moderate to severe pain without any known side effects. [8, 9] It was designed by a simplification of the structure of morphine that kept the pharmacophoric elements responsible for the analgesic effect. Herein, we describe the isolation of tramadol from the root bark of N. latifolia, and the different methods used to prove the authenticity of its natural origin. The
Published: 2013
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27. A Model of Smart G-Quadruplex Ligand

Author: Romain Haudecoeur, Franck Denat, Loic Stefan, David Monchaud, Département de pharmacochimie moléculaire (DPM), Université Grenoble Alpes (UGA)-Université Joseph Fourier - Grenoble 1 (UJF)-Centre National de la Recherche Scientifique (CNRS), Institut de Chimie Moléculaire de l'Université de Bourgogne [Dijon] (ICMUB), Université de Bourgogne (UB)-Centre National de la Recherche Scientifique (CNRS), Conception, synthèse et vectorisation de biomolécules. (CSVB), Institut Curie-Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF), Université de Bourgogne (UB)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), and Université Paris Descartes - Paris 5 (UPD5)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut Curie [Paris]
Subjects: Models, Molecular, 0303 health sciences, Magnetic Resonance Spectroscopy, Dose-Response Relationship, Drug, Stereochemistry, Ligand, Chemistry, General Chemistry, Nuclear magnetic resonance spectroscopy, 010402 general chemistry, G-quadruplex, Ligands, 01 natural sciences, Biochemistry, Catalysis, 0104 chemical sciences, G-Quadruplexes, Small Molecule Libraries, 03 medical and health sciences, Colloid and Surface Chemistry, [CHIM]Chemical Sciences, heterocyclic compounds, Selectivity, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology
Abstract: An unprecedented strategy to control the quadruplex- vs duplex-DNA selectivity of a ligand is reported. We designed a compound whose structure can rearrange when it interacts with a G-quadruplex, thereby controlling its affinity. Thus, the first "smart G-quadruplex ligand" is reported, since this ligand experiences a structural change in the presence of quadruplexes but not in the presence of duplexes, ensuring a high level of quadruplex selectivity.
Published: 2012
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28. ChemInform Abstract: Recent Advances in the Medicinal Chemistry of Aurones

Author: Romain Haudecoeur and Ahcène Boumendjel
Subjects: Chemistry, General Medicine, Medicinal chemistry
Abstract: The first review regarding the potential of aurones as promising drug candidates was reported in 2003. Since, considerable efforts have been made to explore the pharmacological and therapeutical activities of aurones. In this regard, many biological areas were concerned, including major pathological, such as cancer and neurodegenerative disorders. The aim of the present report is to highlight the progress made during the last ten years on the medicinal chemistry of aurones. A special focus will be made on the structure-activity relationship aspects among aurones and especially in case where aurones were found highly active than the corresponding flavones and chalcones.
Published: 2012
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29. Porphyrin-templated synthetic G-quartet (PorphySQ): a second prototype of G-quartet-based G-quadruplex ligand

Author: Hai-Jun Xu, Romain Haudecoeur, Jean-Michel Barbe, Franck Denat, David Monchaud, Claude P. Gros, Loic Stefan, Sophie Vuong, Philippe Richard, Institut de Chimie Moléculaire de l'Université de Bourgogne [Dijon] (ICMUB), Université de Bourgogne (UB)-Centre National de la Recherche Scientifique (CNRS), Département de pharmacochimie moléculaire (DPM), Université Grenoble Alpes (UGA)-Université Joseph Fourier - Grenoble 1 (UJF)-Centre National de la Recherche Scientifique (CNRS), Synthèse Organique (E5), Institut de Chimie des Milieux et Matériaux de Poitiers (IC2MP), Université de Poitiers-Centre National de la Recherche Scientifique (CNRS)-Université de Poitiers-Centre National de la Recherche Scientifique (CNRS), Journaliste, AFP, Conception, synthèse et vectorisation de biomolécules. (CSVB), Institut Curie-Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5), Université de Bourgogne (UB)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF), Université de Poitiers-Institut national des sciences de l'Univers (INSU - CNRS)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université de Poitiers-Institut national des sciences de l'Univers (INSU - CNRS)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), and Université Paris Descartes - Paris 5 (UPD5)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut Curie [Paris]
Subjects: Models, Molecular, 0303 health sciences, Porphyrins, Stereochemistry, Organic Chemistry, Hydrogen Bonding, 010402 general chemistry, G-quadruplex, Ligands, 01 natural sciences, Biochemistry, Porphyrin, 0104 chemical sciences, G-Quadruplexes, 03 medical and health sciences, chemistry.chemical_compound, chemistry, Intramolecular force, [CHIM]Chemical Sciences, Physical and Theoretical Chemistry, DNA, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology
Abstract: Template-assembled synthetic G-quartet (TASQ) has been reported recently as a G-quadruplex ligand interacting with DNA according to an unprecedented, nature-inspired ‘like likes like’ approach, based on the association between two G-quartets, one being native (quadruplex) and the other one artificial (ligand). Herein, a novel TASQ-based ligand is designed, synthesized and its quadruplex-recognition properties are evaluated in vitro: PorphySQ (for porphyrin-templated synthetic G-quartet) displays enhanced quadruplex recognition properties as compared to the very first reported prototype (DOTASQ, for DOTA-templated synthetic G-quartet), since the porphyrin template insures a more stable intramolecular G-quartet fold due to self-stabilizing interactions that may take place intramolecularly between the porphyrin ring and the formed G-quartet.
Published: 2012
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30. Versatile effects of aurone structure on mushroom tyrosinase activity

Author: Carole Dubois, Maylis Orio, Ahcène Boumendjel, Marius Réglier, Renaud Hardré, Catherine Belle, Hélène Jamet, Constance Bochot, Romain Haudecoeur, Institut des Sciences Moléculaires de Marseille (ISM2), Aix Marseille Université (AMU)-École Centrale de Marseille (ECM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Département de pharmacochimie moléculaire (DPM), Université Joseph Fourier - Grenoble 1 (UJF)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Laboratoire Avancé de Spectroscopie pour les Intéractions la Réactivité et l'Environnement - UMR 8516 (LASIRE), Institut de Chimie du CNRS (INC)-Université de Lille-Centre National de la Recherche Scientifique (CNRS), Département de Chimie Moléculaire - Chimie Inorganique Redox (DCM - CIRE), Département de Chimie Moléculaire (DCM), Université Joseph Fourier - Grenoble 1 (UJF)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF), Institut de Chimie du CNRS (INC)-Université de Lille-Centre National de la Recherche Scientifique (CNRS)-Centrale Lille Institut (CLIL), and Département de Chimie Moléculaire - Chimie Inorganique Redox Biomimétique (DCM - CIRE)
Subjects: Models, Molecular, Stereochemistry, Pyridines, Tyrosinase, Stereoisomerism, 010402 general chemistry, DFT calculations, 01 natural sciences, Biochemistry, Cyclic N-Oxides, 03 medical and health sciences, chemistry.chemical_compound, Structure-Activity Relationship, enzyme activators, Aurone, Structure–activity relationship, Molecule, Moiety, Chelation, Enzyme Inhibitors, Molecular Biology, 030304 developmental biology, Benzofurans, 0303 health sciences, Mushroom, Molecular Structure, Chemistry, Monophenol Monooxygenase, Organic Chemistry, 0104 chemical sciences, [CHIM.THEO]Chemical Sciences/Theoretical and/or physical chemistry, Enzyme Activation, aurone, Molecular Medicine, Agaricales, mushroom tyrosinase
Abstract: Elucidation of the binding modes of Ty inhibitors is an important step for in-depth studies on how to regulate tyrosinase activity. In this paper we highlight the extraordinarily versatile effects of the aurone structure on mushroom Ty activity. Depending on the position of the OH group on the B-ring, aurones can behave either as substrates or as hyperbolic activators. The synthesis of a hybrid aurone through combination of an aurone moiety with HOPNO (2-hydroxypyridine N-oxide), a good metal chelate, led us to a new, efficient, mixed inhibitor for mushroom tyrosinase. Another important feature pointed out by our study is the presence of more than one site for aurone compounds on mushroom tyrosinase. Because study of the binding of the hybrid aurone was difficult to perform with the enzyme, we undertook binding studies with tyrosinase functional models in order to elucidate the binding mode (chelating vs. bridging) on a dicopper(II) center. Use of EPR combined with theoretical DFT calculations allowed us to propose a preferred chelating mode for the interaction of the hybrid aurone with a dicopper(II) center.
Published: 2011
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31. Discovery of Naturally Occurring Aurones That Are Potent Allosteric Inhibitors of Hepatitis C Virus RNA-Dependent RNA Polymerase

Author: Coralie Pallier, Antoine Fortuné, Edwige Nicolle, Ahcène Boumendjel, Catherine Belle, Abdelhakim Ahmed-Belkacem, Romain Haudecoeur, Jean-Michel Pawlotsky, Wei Yi, Rozenn Brillet, Guellaen, Georges, Département de pharmacochimie moléculaire (DPM), Université Joseph Fourier - Grenoble 1 (UJF)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Département de Chimie Moléculaire (DCM), Laboratoire de virologie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre, Centre National de Référence Virus des hépatites B, C et Delta, Institut National de la Transfusion Sanguine [Paris] (INTS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), R. H. is a recipient of a fellowship grant from the Ministère de l'Enseignement et de la Recherche to whom he is very thankful. A part of the project related to this article is funded by l'Agence Nationale de la Recherche (ANR). W.Y is a recipient of a fellowship from the University of Sun Yat-Sen (China) to whom he is thankful., Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-IFR10, and Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université Joseph Fourier - Grenoble 1 (UJF)
Subjects: Models, Molecular, Stereochemistry, Hepacivirus, Hepatitis C virus, viruses, Allosteric regulation, RNA-dependent RNA polymerase, 010402 general chemistry, medicine.disease_cause, Antiviral Agents, 01 natural sciences, Article, chemistry.chemical_compound, RNA polymerase, Drug Discovery, Aurone, medicine, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Benzofurans, biology, 010405 organic chemistry, Mutagenesis, RNA-Dependent RNA Polymerase, biology.organism_classification, Enzyme assay, 0104 chemical sciences, 3. Good health, chemistry, biology.protein, Molecular Medicine
Abstract: International audience; We have identified naturally occurring 2-benzylidenebenzofuran-3-ones (aurones) as new templates for non-nucleoside hepatitis C virus (HCV) RNA-dependent RNA polymerase (RdRp) inhibitors. The aurone target site, identified by site-directed mutagenesis, is located in thumb pocket I of HCV RdRp. The RdRp inhibitory activity of 42 aurones was rationally explored in an enzyme assay. Molecular docking studies were used to determine how aurones bind to HCV RdRp and to predict their range of inhibitory activity. Seven aurone derivatives were found to have potent inhibitory effects on HCV RdRp, with IC(50) below 5 μM and excellent selectivity index (inhibition activity versus cellular cytotoxicity). The most active aurone analogue was (Z)-2-((1-butyl-1H-indol-3-yl)methylene)-4,6-dihydroxybenzofuran-3(2H)-one (compound 51), with an IC(50) of 2.2 μM. Their potent RdRp inhibitory activity and their low toxicity make these molecules attractive candidates as direct-acting anti-HCV agents.
Published: 2011
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32. WS23.1 Models of the 3D structure of CFTR: from the understanding of the protein functions to the design of correctors

Author: Mathilde Jollivet, Isabelle Callebaut, Pierre Lehn, Antoine Fortuné, Jean-Paul Mornon, Frédéric Becq, Brice Hoffmann, Jean-Luc Décout, Romain Haudecoeur, Clément Boinot, and B. Boucherie
Subjects: Pulmonary and Respiratory Medicine, business.industry, Pediatrics, Perinatology and Child Health, Medicine, Pediatrics, Perinatology, and Child Health, business, Humanities
Abstract: B. Hoffmann1, J.-P. Mornon1, B. Boucherle2, A. Fortune2, R. Haudecoeur2, C. Boinot3, M. Jollivet3, J.-L. Decout2, F. Becq3, P. Lehn4, I. Callebaut1. 1Universite Pierre et Marie Curie, CNRS, MNHN, IRD, IMPMC, UMR 7590, Paris, France; 2Universite Joseph Fourier, UJF/CNRS, DPM, UMR 5063, Grenoble, France; 3Universite de Poitiers, CNRS, Laboratoire STIM, ERL 7368, Poitiers, France; 4Universite de Bretagne Occidentale, INSERM U 1078, Brest, France
Published: 2014
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33. Recombinant Tyrosinase from Polyporus arcularius : Overproduction in Escherichia coli , Characterization, and Use in a Study of Aurones as Tyrosinase Effectors

Author: Romain Haudecoeur, Ahcène Boumendjel, Petr Man, Alena Křenková, Marius Réglier, Eva Marková, Yasmina Mekmouche, Ludmila Martínková, Renaud Hardré, Michael Kotik, Elise Courvoisier-Dezord, Institute of Microbiology of the Czech Academy of Sciences (MBU / CAS), Czech Academy of Sciences [Prague] (CAS), Department of Biochemistry and Microbiology, Faculty of Food and Biochemical Technology, ICT Prague-Technicka 3, Département de pharmacochimie moléculaire (DPM ), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Institut des Sciences Moléculaires de Marseille (ISM2), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS)-École Centrale de Marseille (ECM)-Institut de Chimie du CNRS (INC), REGLIER, Marius, Institute of Microbiology of the Czech Academy of Sciences [Prague, Czech Republic] (MBU / CAS), and Aix Marseille Université (AMU)-École Centrale de Marseille (ECM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)
Subjects: 0106 biological sciences, 0301 basic medicine, [CHIM.INOR] Chemical Sciences/Inorganic chemistry, Tyrosinase, Gene Expression, [CHIM.INOR]Chemical Sciences/Inorganic chemistry, medicine.disease_cause, 01 natural sciences, Fungal Proteins, 03 medical and health sciences, Enzyme activator, 010608 biotechnology, medicine, Escherichia coli, [CHIM.COOR]Chemical Sciences/Coordination chemistry, ComputingMilieux_MISCELLANEOUS, Polyporus arcularius, Benzofurans, chemistry.chemical_classification, Fungal protein, biology, Effector, Monophenol Monooxygenase, [CHIM.ORGA]Chemical Sciences/Organic chemistry, General Chemistry, [CHIM.COOR] Chemical Sciences/Coordination chemistry, biology.organism_classification, [CHIM.ORGA] Chemical Sciences/Organic chemistry, Polyporus, Recombinant Proteins, Kinetics, 030104 developmental biology, Enzyme, Biochemistry, chemistry, General Agricultural and Biological Sciences
Abstract: Tyrosinases act in the development of organoleptic properties of tea, raisins, etc., but also cause unwanted browning of fruits, vegetables, and mushrooms. The tyrosinase from Agaricus bisporus has been used as a model to study tyrosinase inhibitors, which are also indispensable in the treatment of skin pigmentation disorders. However, this model has disadvantages such as side enzyme activities and the presence of multiple isoenzymes. Therefore, we aimed to introduce a new tyrosinase model. The pro-tyrosinase from Polyporus arcularius was overproduced in Escherichia coli. Trypsin digestion led to a cleavage after R388 and hence enzyme activation. The tyrosinase was a homodimer and transformed L-DOPA and tert-butylcatechol preferentially. Various aurons were examined as effectors of this enzyme. 2'- and 3'-hydroxyaurones acted as its activators and 2',4'-dihydroxyaurone as an inhibitor, whereas 4'-hydroxyaurones were its substrates. The enzyme is a promising model for tyrosinase effector studies, being a single isoenzyme and void of side enzyme activities.

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33 results on '"Romain Haudecoeur"'

1. Design and Synthesis of Novel Amino and Acetamidoaurones with Antimicrobial Activities

2. Synthetic G-Quartets as Versatile Nanotools for the Luminescent Detection of G-Quadruplexes

3. Bioactive Aurones, Indanones, and Other Hemiindigoid Scaffolds: Medicinal Chemistry and Photopharmacology Perspectives

4. Resorcinol-based hemiindigoid derivatives as human tyrosinase inhibitors and melanogenesis suppressors in human melanoma cells

5. β-Carboline as a Privileged Scaffold for Multitarget Strategies in Alzheimer’s Disease Therapy

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8. A One-Pot Synthesis of Highly Functionalized Purines

9. Occurrences, biosynthesis and properties of aurones as high-end evolutionary products

10. Aurone derivatives as promising antibacterial agents against resistant Gram-positive pathogens

11. Piperidinyl-embeded chalcones possessing anti PI3Kδ inhibitory properties exhibit anti-atopic properties in preclinical models

12. Glycosyl-Substituted Dicarboxylates as Detergents for the Extraction, Overstabilization, and Crystallization of Membrane Proteins

13. Traditional uses, phytochemistry and pharmacological properties of African Nauclea species: A review

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18. Structure-Activity Relationships in the Development of Allosteric Hepatitis C Virus RNA-Dependent RNA Polymerase Inhibitors: Ten Years of Research

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20. Refinement of arylthiosemicarbazone pharmacophore in inhibition of mushroom tyrosinase

21. Synthetic G-Quartets as Versatile Nanotools for the Luminescent Detection of G-Quadruplexes

22. Biomimetic synthesis of Tramadol

23. Investigation of Binding-Site Homology between Mushroom and Bacterial Tyrosinases by Using Aurones as Effectors

24. B-ring modified aurones as promising allosteric inhibitors of hepatitis C virus RNA-dependent RNA polymerase

25. Multitasking Water-Soluble Synthetic G-Quartets: From Preferential RNA-Quadruplex Interaction to Biocatalytic Activity

26. Occurrence of the Synthetic Analgesic Tramadol in an African Medicinal Plant

27. A Model of Smart G-Quadruplex Ligand

28. ChemInform Abstract: Recent Advances in the Medicinal Chemistry of Aurones

29. Porphyrin-templated synthetic G-quartet (PorphySQ): a second prototype of G-quartet-based G-quadruplex ligand

30. Versatile effects of aurone structure on mushroom tyrosinase activity

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32. WS23.1 Models of the 3D structure of CFTR: from the understanding of the protein functions to the design of correctors

33. Recombinant Tyrosinase from Polyporus arcularius : Overproduction in Escherichia coli , Characterization, and Use in a Study of Aurones as Tyrosinase Effectors

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