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9 results on '"Céline Ballandonne"'

1. Design, synthesis, and pharmacological evaluation of multitarget-directed ligands with both serotonergic subtype 4 receptor (5-HT4R) partial agonist and 5-HT6R antagonist activities, as potential treatment of Alzheimer’s disease

Author

Céline Ballandonne, Jana Sopkova-de Oliveira Santos, Samir Yahiaoui, Thomas Freret, Patrick Dallemagne, Christophe Rochais, Audrey Davis, Katia Hamidouche, Michel Boulouard, 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), Université de Caen Normandie - UFR Santé (UNICAEN Santé), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU), Centre d'Etudes et de Recherche sur le Médicament de Normandie (CERMN), and Groupe Mémoire et Plasticité comportementale (GMPc)

Subjects
Male, 5-HT(4) receptors agonists, 0301 basic medicine, Agonist, medicine.medical_specialty, medicine.drug_class, Guinea Pigs, Chemistry Techniques, Synthetic, [CHIM.THER]Chemical Sciences/Medicinal Chemistry, Pharmacology, Ligands, Serotonergic, Partial agonist, MTDL, Mice, Serotonin 5-HT4 Receptor Agonists, 03 medical and health sciences, 0302 clinical medicine, Piperidines, Alzheimer Disease, Internal medicine, Drug Discovery, medicine, Animals, Humans, Molecular Targeted Therapy, Receptor, 5-HT receptor, Aniline Compounds, Chemistry, Organic Chemistry, Antagonist, General Medicine, 5-HT(6) receptors antagonists, medicine.disease, 3. Good health, HEK293 Cells, 030104 developmental biology, Endocrinology, Drug Design, Receptors, Serotonin, Receptors, Serotonin, 5-HT4, Serotonin Antagonists, Alzheimer's disease, Alzheimer’s disease, 030217 neurology & neurosurgery
Abstract

International audience; 5-HT4 receptor (5-HT4R) activation and blockade of the 5-HT6 receptor (5-HT6R) are known to enhance the release of numerous neurotransmitters whose depletion is implicated in Alzheimer's disease (AD). Furthermore, 5-HT4R agonists seem to favor production of the neurotrophic soluble amyloid protein precursor alpha (sAPPα). Consequently, combining 5-HT4R agonist/5-HT6R antagonist activities in a single chemical compound would constitute a novel approach able to display both a symptomatic and disease-modifying effect in AD. Seventeen novel derivatives of RS67333 (1) were synthesized and evaluated as potential dual-target compounds. Among them, four agents showed nanomolar and submicromolar affinities toward 5-HT4R and 5-HT6R, respectively; one of them, 7m, was selected on the basis of its in vitro affinity (Ki5-HT4R = 5.3 nM, Ki5-HT6R = 219 nM) for further in vivo experiments, where 7m showed an antiamnesic effect in the mouse at 1 mg/kg ip

Published
2016
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2. Synthesis and evaluation of novel serotonin 4 receptor radiotracers for single photon emission computed tomography

Author

Christophe Rochais, Audrey Davis, Sophie Corvaisier, Thomas Cailly, Cédric Lecoutey, Céline Ballandonne, Frédéric Fabis, Benjamin B. Tournier, Patrick Dallemagne, Philippe Millet, Marc Since, Julien Lalut, Centre d'Etudes et de Recherche sur le Médicament de Normandie (CERMN), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU), and Hôpitaux Universitaires de Genève (HUG)

Subjects
0301 basic medicine, Serotonin, Benzamides/chemical synthesis/chemistry, Radioligand, Analytical chemistry, Molecular imaging, 5-HT4, [CHIM.THER]Chemical Sciences/Medicinal Chemistry, Chemistry Techniques, Synthetic, Single-photon emission computed tomography, Iodine Radioisotopes, Rats, Sprague-Dawley, 03 medical and health sciences, chemistry.chemical_compound, ddc:616.89, 0302 clinical medicine, Receptors, Serotonin, 5-HT4/metabolism, Drug Discovery, medicine, Animals, Humans, Radioactive Tracers, Receptor, Benzamide, 5-HT receptor, Pharmacology, Tomography, Emission-Computed, Single-Photon, medicine.diagnostic_test, Ligand, Chemistry, Organic Chemistry, General Medicine, Ketones, Tomography, Emission-Computed, Single-Photon/methods, Rats, 030104 developmental biology, SPECT, Lipophilicity, Benzamides, Biophysics, Receptors, Serotonin, 5-HT4, Ketones/chemical synthesis/chemistry, 030217 neurology & neurosurgery
Abstract

International audience; Despite its implication in several physiological and pathological processes the serotonin subtype-4 receptor (5-HT4R) has seen limited effort for the development of radiolabeling agent especially concerning single photon emission computed tomography (SPECT). Bearing an ester function, the available ligands are rapidly susceptible to hydrolysis which limits their use in vivo. In this study the synthesis of iodinated benzamide and ketone analogs were described. Their affinity for the 5-HT4R and their lipophilicity were evaluated and the most promising derivatives were evaluated ex vivo for their binding to the receptor and for their ability to displace the reference ligand [125I]-SB207710.

Published
2016
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3. Synthesis and structure-affinity relationships of selective high-affinity 5-HT(4) receptor antagonists: application to the design of new potential single photon emission computed tomography tracers

Author

Fabienne Dulin, Noé Dumas, Céline Ballandonne, Christine Fossey, Thomas Cailly, Emmanuelle Dubost, Frédéric Fabis, Rosa Magnelli, Jana Sopkova de-Oliveira Santos, Sabrina Butt-Gueulle, Philippe Millet, Yves Charnay, Sylvain Rault, Daniel H. Caignard, Centre d'Etudes et de Recherche sur le Médicament de Normandie (CERMN), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU), Université Grenoble Alpes - UFR Pharmacie (UGA UFRP), Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Embedded System Lab (ESL), Thales Research and Technology, and Hôpitaux Universitaires de Genève (HUG)

Subjects
Serotonin 5-HT4 Receptor Antagonists, Piperidines/pharmacology, Stereochemistry, chemistry.chemical_element, Serotonin 5-HT4 Receptor Antagonists/chemical synthesis/pharmacology, [CHIM.THER]Chemical Sciences/Medicinal Chemistry, Ligands, 010402 general chemistry, 01 natural sciences, Article, Dioxanes, Iodine Radioisotopes, Mice, Radioligand Assay, Structure-Activity Relationship, chemistry.chemical_compound, Piperidines, In vivo, Drug Discovery, medicine, Animals, Humans, Receptor, 5-HT receptor, Tomography, Emission-Computed, Single-Photon, Phenanthridine, medicine.diagnostic_test, Dioxanes/pharmacology, 010405 organic chemistry, Antagonist, 0104 chemical sciences, chemistry, Drug Design, Molecular Probes, Fluorine, Molecular Medicine, Receptors, Serotonin, 5-HT4, Receptors, Serotonin, 5-HT4/chemistry/metabolism, Radiopharmaceuticals, Selectivity, Emission computed tomography
Abstract

The work described herein aims at finding new potential ligands for the brain imaging of 5-HT(4) receptors (5-HT(4)Rs) using single-photon emission computed tomography (SPECT). Starting from the nonsubstituted phenanthridine compound 4a, exhibiting a K(i) value of 51 nM on the 5-HT(4)R, we explored the structure-affinity in this series. We found that substitution in position 4 of the tricycle with a fluorine atom gave the best result. Introduction of an additional nitrogen atom inside the tricyclic framework led to an increase of both the affinity and selectivity for 5-HT(4)R, suggesting the design of the antagonist 4v, exhibiting a high affinity of 0.04 nM. Several iodinated analogues were then synthesized as potential SPECT tracers. The iodinated compound 11d was able to displace the reference radioiodinated 5-HT(4)R antagonist (1-butylpiperidin-4-yl)methyl-8-amino-7-iodo[(123)I]-2,3-dihydrobenzo[b][1,4]dioxine-5-carboxylate {[(123)I]1, [(123)I]SB 207710} both in vitro and in vivo in brain. Compound 11d was radiolabeled with [(125)I]iodine, providing a potential SPECT candidate for brain imaging of 5-HT(4)R.

Published
2012
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4. Design of a serotonin 4 receptor radiotracer with decreased lipophilicity for single photon emission computed tomography

Author

Céline Ballandonne, Frédéric Fabis, Noé Dumas, Philippe Millet, Aurélien Lesnard, Christine Fossey, Jean-Philippe Bouillon, Benjamin B. Tournier, Yves Charnay, Nathalie Fresneau, Thomas Cailly, Chimie Organique et Bioorganique : Réactivité et Analyse (COBRA), Institut Normand de Chimie Moléculaire Médicinale et Macromoléculaire (INC3M), Institut de Chimie du CNRS (INC)-École Nationale Supérieure d'Ingénieurs de Caen (ENSICAEN), Normandie Université (NU)-Normandie Université (NU)-Institut national des sciences appliquées Rouen Normandie (INSA Rouen Normandie), Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Institut National des Sciences Appliquées (INSA)-Université Le Havre Normandie (ULH), Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Centre National de la Recherche Scientifique (CNRS)-Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Institut de Chimie du CNRS (INC)-École Nationale Supérieure d'Ingénieurs de Caen (ENSICAEN), Normandie Université (NU)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie Organique Fine (IRCOF), Université de Rouen Normandie (UNIROUEN), Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Hôpitaux Universitaires de Genève (HUG), Centre d'Etudes et de Recherche sur le Médicament de Normandie (CERMN), Université de Caen Normandie (UNICAEN), and Normandie Université (NU)-Normandie Université (NU)

Subjects
Serotonin, Stereochemistry, 5-HT, Molecular imaging, [CHIM.THER]Chemical Sciences/Medicinal Chemistry, Single-photon emission computed tomography, Ligands, Iodine Radioisotopes, 03 medical and health sciences, chemistry.chemical_compound, Structure-Activity Relationship, ddc:616.89, 0302 clinical medicine, In vivo, Spect imaging, Drug Discovery, medicine, Humans, 5-HT receptor, 030304 developmental biology, Pharmacology, Tomography, Emission-Computed, Single-Photon, 0303 health sciences, Phenanthridine, medicine.diagnostic_test, Dose-Response Relationship, Drug, Molecular Structure, Organic Chemistry, Brain, General Medicine, 3. Good health, Phenanthridines, chemistry, Drug Design, SPECT, Lipophilicity, Biophysics, Receptors, Serotonin, 5-HT4, Radiopharmaceuticals, 030217 neurology & neurosurgery, Radiolabeling, Iodine
Abstract

International audience; With the aim to develop a suitable radiotracer for the brain imaging of the serotonin 4 receptor subtype (5-HT4R) using single photon emission computed tomography (SPECT), we synthesized and evaluated a library of di- and triazaphenanthridines with lipophilicity values which were in the range expected to favour brain penetration, and which demonstrated specific binding to the target of interest. Adding additional nitrogen atoms to previously described phenanthridine ligands exhibiting a high unspecific binding, we were able to design a radioiodinated compound [125I]14. This compound exhibited a binding affinity value of 0.094 nM toward human 5-HT4R and a high selectivity over other serotonin receptor subtypes (5-HTR). In vivo SPECT imaging studies and competition experiments demonstrated that the decreased lipophilicity (in comparison with our previously reported compounds 4 and 5) allowed a more specific labelling of the 5-HT4R brain-containing regions.

Published
2015
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5. Novel Multitarget-Directed Ligands (MTDLs) with Acetylcholinesterase (AChE) Inhibitory and Serotonergic Subtype 4 Receptor (5-HT 4 R) Agonist Activities As Potential Agents against Alzheimer’s Disease: The Design of Donecopride

Author

Sylvie Claeysen, Michel Boulouard, Emmanuelle Dubost, Valentine Bouet, David Genest, Céline Ballandonne, Rémi Legay, Patrick Dallemagne, Damien Hedou, Samir Yahiaoui, Thomas Freret, Jana Sopkova-de Oliveira Santos, François Dauphin, Katia Hamidouche, Patrizia Giannoni, Florence Gaven, Christophe Rochais, Sophie Corvaisier, Aurélie Malzert-Fréon, Cédric Lecoutey, Centre d'Etudes et de Recherche sur le Médicament de Normandie (CERMN), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU), Institut de Génomique Fonctionnelle (IGF), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Groupe Mémoire et Plasticité comportementale (GMPc), This work was supported by funding from the Conseil Régional de Basse Normandie, France (Dispositif de Soutien aux Projets de Recherche Emergents), French Agence Nationale de la Recherche Projects MALAD ANR-12-JS007-0012-01 and ADAMGUARD ANR-12-BSV4-008-01, and Ligue Européenne Contre la Maladie d’Alzheimer Grant 12721., ANR-12-JS07-0012,MALAD,Developpement de Ligands pluriactifs d'intérêt potentiel dans le traitement de la maladie d'Alzheimer(2012), ANR-12-BSV4-0008,ADAMGUARD,Les réseaux protéiques associés aux récepteurs 5 HT4 : gardes rapprochées du trafic de l'ADAM10 et de l'APP(2012), Cailly, Thomas, Jeunes Chercheuses et Jeunes Chercheurs - Developpement de Ligands pluriactifs d'intérêt potentiel dans le traitement de la maladie d'Alzheimer - - MALAD2012 - ANR-12-JS07-0012 - JC - VALID, BLANC - Les réseaux protéiques associés aux récepteurs 5 HT4 : gardes rapprochées du trafic de l'ADAM10 et de l'APP - - ADAMGUARD2012 - ANR-12-BSV4-0008 - BLANC - VALID, and Université de Montpellier (UM)-Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 2 - Sciences et Techniques (UM2)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Agonist, Male, medicine.drug_class, Aché, [CHIM.THER] Chemical Sciences/Medicinal Chemistry, Guinea Pigs, Drug Evaluation, Preclinical, Mice, Inbred Strains, [CHIM.THER]Chemical Sciences/Medicinal Chemistry, Pharmacology, Serotonergic, Inhibitory postsynaptic potential, Crystallography, X-Ray, Ligands, Alzheimer's Disease, MTDL, chemistry.chemical_compound, Serotonin 5-HT4 Receptor Agonists, Structure-Activity Relationship, Piperidines, In vivo, Alzheimer Disease, Drug Discovery, medicine, Toxicity Tests, Acute, Structure–activity relationship, Animals, Humans, Computer Simulation, Molecular Targeted Therapy, Receptor, Aniline Compounds, Acetylcholinesterase, language.human_language, 3. Good health, Donecopride, Mice, Inbred C57BL, Memory, Short-Term, chemistry, Drug Design, language, Molecular Medicine, Cholinesterase Inhibitors, Receptors, Serotonin, 5-HT4, 5-HT4 Receptors
Abstract

International audience; In this work, we describe the synthesis and in vitro evaluation of a novel series of multitarget-directed ligands (MTDL) displaying both nanomolar dual-binding site (DBS) acetylcholinesterase inhibitory effects and partial 5-HT4R agonist activity, among which donecopride was selected for further in vivo evaluations in mice. The latter displayed procognitive and antiamnesic effects and enhanced sAPPα release, accounting for a potential symptomatic and disease-modifying therapeutic benefit in the treatment of Alzheimer’s disease.

Published
2015
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6. Synthesis and evaluation of cytotoxic activities of new guanidines derived from carbazoles

Author

Thierry Cresteil, Céline Ballandonne, Patrick Dallemagne, Hussein El-Kashef, Aurélien Lesnard, Maria Stefania Sinicropi, Sylvain Rault, Jean-Charles Lancelot, Geneviève Aubert, Anna Caruso, Carmela Saturnino, Centre d'Etudes et de Recherche sur le Médicament de Normandie ( CERMN ), Université de Caen Normandie ( UNICAEN ), Normandie Université ( NU ) -Normandie Université ( NU ), Institut de Chimie des Substances Naturelles ( ICSN ), Centre National de la Recherche Scientifique ( CNRS ), Centre d'Etudes et de Recherche sur le Médicament de Normandie (CERMN), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU), Institut de Chimie des Substances Naturelles (ICSN), and Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)

Subjects
Clinical Biochemistry, Carbazoles, Drug Evaluation, Preclinical, Pharmaceutical Science, HL-60 Cells, Biochemistry, Guanidines, chemistry.chemical_compound, [ CHIM.ORGA ] Chemical Sciences/Organic chemistry, Drug Discovery, Cytotoxic T cell, Organic chemistry, Humans, Cytotoxicity, Molecular Biology, ComputingMilieux_MISCELLANEOUS, Cell Proliferation, Dose-Response Relationship, Drug, Chemistry, Carbazole, [CHIM.ORGA]Chemical Sciences/Organic chemistry, Cytotoxins, Organic Chemistry, [ CHIM.THER ] Chemical Sciences/Medicinal Chemistry, HCT116 Cells, Combinatorial chemistry, Thiourea, MCF-7 Cells, Molecular Medicine
Abstract

International audience; Several new alkylguanidines derived from carbazole have been synthesized in a simple one-pot reaction starting from 3-aminocarbazole derivatives. The aminocarbazoles were reacted with ethoxycarbonylisothiocyanate, to give thiourea intermediates, followed by the addition of an alkylamine and HgCl2 to give ethoxycarbonylguanidine intermediates. The reaction mixture was then heated at 160°C to give the N-(1,4-dimethyl-9H-carbazol-3-yl)-N'-alkylguanidines. The cytotoxic activity of all the synthesized guanidines was evaluated against different cell lines.

Published
2014
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7. Discovery of a new antileishmanial hit in 8-nitroquinoline series

Author

Patrick Dallemagne, Thierry Cresteil, Florence Gaven, Sylvie Claeysen, Patrizia Giannoni, Sophie Corvaisier, Michel Boulouard, Céline Ballandonne, Aurélie Malzert-Fréon, Cédric Lecoutey, Thomas Freret, Christophe Rochais, Valentine Bouet, Damien Hedou, Serge Mignani, and Marc Since

Subjects
Leishmania donovani, Antiprotozoal Agents, Pharmacology, 010402 general chemistry, 01 natural sciences, Mice, parasitic diseases, Drug Discovery, medicine, Animals, Humans, Amastigote, IC50, Miltefosine, Life Cycle Stages, biology, 010405 organic chemistry, Chemistry, Organic Chemistry, Nitroquinolines, General Medicine, Hep G2 Cells, biology.organism_classification, In vitro, 0104 chemical sciences, 3. Good health, Leishmania infantum, Pharmacophore, medicine.drug, Pentamidine
Abstract

A series of nitrated 2-substituted-quinolines was synthesized and evaluated in vitro toward Leishmania donovani promastigotes. In parallel, the in vitro cytotoxicity of these molecules was assessed on the murine J774 and human HepG2 cell lines. Thus, a very promising antileishmanial hit molecule was identified (compound 21), displaying an IC(50) value of 6.6 μM and CC(50) values ≥ 100 μM, conferring quite good selectivity index to this molecule, in comparison with 3 drug-compounds of reference (amphotericin B, miltefosine and pentamidine). Compound 21 also appears as an efficient in vitro antileishmanial molecule against both Leishmania infantum promastigotes and the intracellular L. donovani amastigotes (respective IC(50) = 7.6 and 6.5 μM). Moreover, hit quinoline 21 does not show neither significant antiplasmodial nor antitoxoplasmic in vitro activity and though, presents a selective antileishmanial activity. Finally, a structure-activity relationships study enabled to define precisely the antileishmanial pharmacophore based on this nitroquinoline scaffold: 2-hydroxy-8-nitroquinoline.

Published
2012

8. Synthesis of dual AChE/5-HT4 receptor multi-target directed ligands

Author

Céline Ballandonne, Jana Sopkova-de Oliveira Santos, Cédric Lecoutey, Fabienne Dulin, Sophie Corvaisier, Christophe Rochais, Alban Lepailleur, Sabrina Butt-Gueulle, Patrick Dallemagne, David Genest, Centre d'Etudes et de Recherche sur le Médicament de Normandie ( CERMN ), Université de Caen Normandie ( UNICAEN ), Normandie Université ( NU ) -Normandie Université ( NU ), Centre d'Etudes et de Recherche sur le Médicament de Normandie (CERMN), Université de Caen Normandie (UNICAEN), and Normandie Université (NU)-Normandie Université (NU)

Subjects
Agonist, Aché, Stereochemistry, medicine.drug_class, Pharmaceutical Science, 5-HT4 receptor, Pharmacology, 01 natural sciences, Biochemistry, 03 medical and health sciences, Multi target, Drug Discovery, medicine, IC50, Cognitive deficit, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, 0303 health sciences, 010405 organic chemistry, Chemistry, Organic Chemistry, medicine.disease, language.human_language, 3. Good health, 0104 chemical sciences, language, Molecular Medicine, Cholinergic, medicine.symptom, Alzheimer's disease
Abstract

The synthesis of novel pyrrolothienopyrazines has been achieved with the aim to bring together in a sole compound both AChE inhibitory effect and 5-HT4R agonist activity. These Multi-Target Directed Ligands might theoretically alleviate the cognitive deficit in Alzheimer disease by restoring the cholinergic activity and by promoting the non-amyloidogenic formation of sAPPα which seems detrimental to the amyloid aggregation. Some of the synthesized compounds bear for the first time these dual activities and compound 15b appears particularly potent towards both AChE and 5-HT4R targets with IC50 and Ki in nanomolar levels. Although these MTDL behave as 5-HT4R antagonists rather than agonists, these results appear hopeful concerning the design of further MTDL with therapeutic interest in AD treatment.

Published
2012

9. Design, synthesis and biological evaluation of novel indano- and thiaindano-pyrazoles with potential interest for Alzheimer's disease

Author

Jana Sopkova-de Oliveira Santos, Céline Ballandonne, David Genest, Sabrina Butt-Gueulle, Patrick Dallemagne, Rémi Legay, Christophe Rochais, Cédric Lecoutey, and Marc Since

Subjects
Pharmacology, 0303 health sciences, Chemistry, Stereochemistry, Organic Chemistry, Pharmaceutical Science, Biochemistry, Acetylcholinesterase, Combinatorial chemistry, 3. Good health, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Design synthesis, 030220 oncology & carcinogenesis, Drug Discovery, Molecular Medicine, Binding site, Disease treatment, 030304 developmental biology, Biological evaluation
Abstract

The synthesis of eighteen novel (thia)indanopyrazole derivatives was achieved starting from amino(thia)indanones. Some of them displayed a dual binding site acetylcholinesterase inhibition which makes them potentially interesting for Alzheimer's disease treatment.

Published
2013
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