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Your search keyword '"Département de pharmacochimie moléculaire (DPM)"' showing total 7 results
Start Over Author "Département de pharmacochimie moléculaire (DPM)" Journal european journal of medicinal chemistry
7 results on '"Département de pharmacochimie moléculaire (DPM)"'

1. 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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2. Exploiting HOPNO-dicopper center interaction to development of inhibitors for human tyrosinase

Author

Elina Buitrago, Clarisse Faure, Marcello Carotti, Elisabetta Bergantino, Renaud Hardré, Marc Maresca, Christian Philouze, Nicolas Vanthuyne, Ahcène Boumendjel, Luigi Bubacco, Amaury du Moulinet d’Hardemare, Hélène Jamet, Marius Réglier, Catherine Belle, Département de Chimie Moléculaire (DCM), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Università degli Studi di Padova = University of Padua (Unipd), 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), Aix Marseille Université (AMU), (ANR-11-LABX-0003-01), Labex Arcane, (ANR-15-IDEX-02), Cosmethics 2.0, and (ANR-17-EURE-003), CBH-EUR-GS

Subjects
Pharmacology, Melanin, Organic Chemistry, Drug Discovery, [CHIM]Chemical Sciences, Inhibitor development, [CHIM.THER]Chemical Sciences/Medicinal Chemistry, General Medicine, Human tyrosinase, Dicopper center
Abstract

International audience; In human, Tyrosinase enzyme (TyH) is involved in the key steps of protective pigments biosynthesis (in skin, eyes and hair). The use of molecules targeting its binuclear copper active site represents a relevant strategy to regulate TyH activities. In this work, we targeted 2-Hydroxypyridine-N-oxide analogs (HOPNO, an established chelating group for the tyrosinase dicopper active site) with the aim to combine effects induced by combination with a reference inhibitor (kojic acid) or natural substrate (tyrosine). The HOPNO-MeOH (3) and the racemic amino acid HOPNO-AA compounds (11) were tested on purified tyrosinases from different sources (fungal, bacterial and human) for comparison purposes. Both 2 compounds have more potent inhibitory activities than the parent HOPNO moiety and display strictly competitive inhibition constant, in particular with human tyrosinase. Furthermore, 11 appears to be the most active on the B16-F1 mammal melanoma cells. The investigations were completed by stereospecificity analysis. Racemic mixture of the fully protected amino acid 10 was separated by chiral HPLC into the corresponding enantiomers. Assignment of the absolute configuration of the deprotected compounds was completed, based on X-ray crystallography. The inhibition activities on melanin production were tested on lysates and whole human melanoma MNT-1 cells. Results showed significant enhancement of the inhibitory effects for the (S) enantiomer compared to the (R) enantiomer. Computational studies led to an explanation of this difference of activity based for both enantiomers on the respective position of the amino acid group versus the HOPNO plane.

Published
2023
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3. 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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4. An expeditious access to 5-pyrimidinol derivatives from cyclic methylglyoxal diadducts, formation of argpyrimidines under physiological conditions and discovery of new CFTR inhibitors

Author

Marie-Carmen Molina, Benjamin Boucherle, Jean-Luc Décout, Brice-Loïc Renard, Bruno Maurin, Caroline Norez, Frédéric Becq, 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 physiologie et biologie cellulaires (IPBC), and Université de Poitiers-Centre National de la Recherche Scientifique (CNRS)

Subjects
Ornithine, Arginine, Stereochemistry, Molecular Conformation, Cystic Fibrosis Transmembrane Conductance Regulator, CHO Cells, 01 natural sciences, Chemical synthesis, Structure-Activity Relationship, 03 medical and health sciences, chemistry.chemical_compound, Cricetulus, Cricetinae, Drug Discovery, Animals, 030304 developmental biology, Pharmacology, 0303 health sciences, Bicyclic molecule, Chemistry, Physical, [CHIM.ORGA]Chemical Sciences/Organic chemistry, 010405 organic chemistry, Organic Chemistry, Methylglyoxal, Stereoisomerism, General Medicine, Pyruvaldehyde, In vitro, 0104 chemical sciences, 3. Good health, Pyrimidines, chemistry, Thiourea, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, Chloride channel
Abstract

IF : 2,88; International audience; In the study of previously reported modulators of CFTR chloride channels that are cyclic methylglyoxal (MG) diadducts (CMGD) to aromatic α-aminoazaheterocycles, we optimized a new expeditious one pot route for preparing in water novel aromatic polycyclic azaheterocycles and described 5-pyrimidinols antioxidants through the formation of 2-oxoaldehyde diadducts to aromatic α-aminoazaheterocycles, amidines, guanidines and thiourea. In regard to the importance as biomarkers of diabetic complications of the 5-pyrimidinols "argpyrimidines" formed in proteins from MG and arginine residues, we demonstrated that argpyrimidines are slowly formed under physiological conditions from CMGD to arginine derivatives according to the synthesis route described. Among the 5-pyrimidinol derivatives prepared, two polycyclic derivatives appeared to inhibit strongly the activity of CFTR channels in wt-CHO cells.

Published
2011
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5. Arylthiosemicarbazones as antileishmanial agents.

Author

Manzano JI, Cochet F, Boucherle B, Gómez-Pérez V, Boumendjel A, Gamarro F, and Peuchmaur M

Subjects
Alkylation, Animals, Antiprotozoal Agents chemistry, Antiprotozoal Agents pharmacology, Cell Line, Humans, Inhibitory Concentration 50, Polycyclic Aromatic Hydrocarbons, Structure-Activity Relationship, Thiosemicarbazones chemistry, Antiprotozoal Agents chemical synthesis, Leishmania donovani drug effects, Thiosemicarbazones pharmacology
Abstract

Based on a screening process, we targeted substituted thiosemicarbazone as potential antileishmanial agents. Our objective was to identify the key structural elements contributing to the anti-parasite activity that might be used for development of effective drugs. A series of 32 compounds was synthesized and their efficacy was evaluated against the clinically relevant intracellular amastigotes of Leishmania donovani. From these, 22 compounds showed EC50 values below 10 μM with the most active derivative (compound 14) showing an EC50 of 0.8 μM with very low toxicity on two different mammalian cell lines. The most relevant structural elements required for higher activity indicate that the presence of a fused bicyclic aromatic ring such as a naphthalene bearing an alkyl or an alkoxy group substituent are prerequisites. Owing to the easy synthesis, high activity and low toxicity, the most active compounds could be considered as a lead for further development., (Copyright © 2016 Elsevier Masson SAS. All rights reserved.)

Published
2016
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6. 2-Indolylmethylenebenzofuranones as first effective inhibitors of ABCC2.

Author

Baiceanu E, Nguyen KA, Gonzalez-Lobato L, Nasr R, Baubichon-Cortay H, Loghin F, Le Borgne M, Chow L, Boumendjel A, Peuchmaur M, and Falson P

Subjects
Animals, Biological Transport drug effects, Dogs, Madin Darby Canine Kidney Cells, Mice, Multidrug Resistance-Associated Protein 2, Multidrug Resistance-Associated Proteins metabolism, NIH 3T3 Cells, Benzofurans chemistry, Benzofurans pharmacology, Multidrug Resistance-Associated Proteins antagonists & inhibitors
Abstract

ABC-transporters play a vital role in drugs bioavailability. They prevent intracellular accumulation of toxic compounds, rendering them a major defense mechanism against harmful substances. In this large family, ABCC2 is an apical efflux pump representing about 10% of all membrane proteins in liver and small intestine, and up to 25% in colon. In these tissues, ABCC2 plays a major role in the pharmacokinetics and pharmacodynamics of endo- and xenobiotics. To gain insight in the function of this crucial protein, we have investigated and developed the first effective inhibitors of this pump. Firstly, we set up a cellular flow cytometry assay for monitoring the drug efflux carried out by ABCC2, and used it for the screening of chemical libraries derived from several chemical classes. We found that 2-indolylmethylenebenzofuranone derivatives as promising candidates. Optimization of the hits provided new compounds that inhibit ABCC2 in the micromolar range, making them the first potent ABCC2 inhibitors reported so far. Such compounds would constitute valuable tools to further investigate the role of ABCC2 in the pharmacokinetics and pharmacodynamics of drugs., (Copyright © 2016 Elsevier Masson SAS. All rights reserved.)

Published
2016
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7. New pseudodimeric aurones as palm pocket inhibitors of Hepatitis C virus RNA-dependent RNA polymerase.

Author

Meguellati A, Ahmed-Belkacem A, Nurisso A, Yi W, Brillet R, Berqouch N, Chavoutier L, Fortuné A, Pawlotsky JM, Boumendjel A, and Peuchmaur M

Subjects
Antiviral Agents chemical synthesis, Antiviral Agents chemistry, Benzofurans chemical synthesis, Benzofurans chemistry, Dose-Response Relationship, Drug, Enzyme Inhibitors chemical synthesis, Enzyme Inhibitors chemistry, Microbial Sensitivity Tests, Molecular Structure, RNA-Dependent RNA Polymerase metabolism, Structure-Activity Relationship, Viral Nonstructural Proteins metabolism, Antiviral Agents pharmacology, Benzofurans pharmacology, Enzyme Inhibitors pharmacology, Hepacivirus enzymology, RNA-Dependent RNA Polymerase antagonists & inhibitors, Viral Nonstructural Proteins antagonists & inhibitors
Abstract

The NS5B RNA-dependent RNA polymerase (RdRp) is a key enzyme for Hepatitis C Virus (HCV) replication. In addition to the catalytic site, this enzyme is characterized by the presence of at least four allosteric pockets making it an interesting target for development of inhibitors as potential anti-HCV drugs. Based on a previous study showing the potential of the naturally occurring aurones as inhibitors of NS5B, we pursued our efforts to focus on pseudodimeric aurones that have never been investigated so far. Hence, 14 original compounds characterized by the presence of a spacer between the benzofuranone moieties were synthesized and investigated as HCV RdRp inhibitors by means of an in vitro assay. The most active inhibitor, pseudodimeric aurone 4, induced high inhibition activity (IC50 = 1.3 μM). Mutagenic and molecular modeling studies reveal that the binding site for the most active derivatives probably is the palm pocket I instead of the thumb pocket I as for the monomeric derivatives., (Copyright © 2016 Elsevier Masson SAS. All rights reserved.)

Published
2016
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