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Your search keyword '"Patrice Agnamey"' showing total 7 results
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7 results on '"Patrice Agnamey"'

1. Design, Synthesis, and In Vitro Antimalarial Evaluation of New 1,3,5-Tris[(4-(Substituted-Aminomethyl)Phenoxy)Methyl]Benzenes

Author

Sandra Albenque-Rubio, Jean Guillon, Patrice Agnamey, Céline Damiani, Solène Savrimoutou, Romain Mustière, Noël Pinaud, Stéphane Moreau, Jean-Louis Mergny, Luisa Ronga, Ioannis Kanavos, Mathieu Marchivie, Serge Moukha, Pascale Dozolme, Pascal Sonnet, and Anita Cohen

Subjects
antimalarial activity, 1,3,5-tris[(4-(substituted-aminomethyl)phenoxy)methyl]benzene, G-quadruplexes, synthesis, Pharmacy and materia medica, RS1-441, Chemistry, QD1-999
Abstract

By taking into account our previously described series of 1,3,5-tris[(4-(substituted-aminomethyl)phenyl)methyl]benzene compounds, we have now designed, prepared, and evaluated in vitro against Plasmodium falciparum a novel series of structural analogues of these molecules, i.e., the 1,3,5-tris[(4-(substituted-aminomethyl)phenoxy)methyl]benzene derivatives. The pharmacological data showed antimalarial activity with IC50 values in the sub and μM range. The in vitro cytotoxicity of these new nitrogen polyphenoxymethylbenzene compounds was also evaluated on human HepG2 cells. The 1,3,5-tris[(4-(substituted-aminomethyl)phenoxy)methyl]benzene derivative 1m was found as one of the most potent and promising antimalarial candidates with favorable cytotoxic to antiprotozoal properties in the P. falciparum strains W2 and 3D7. In conclusion, this 1,3,5-tris[(4-(pyridin-3-ylmethylaminomethyl)phenoxyl)methyl]benzene 1m (IC50 = 0.07 μM on W2, 0.06 μM on 3D7, and 62.11 μM on HepG2) was identified as the most promising antimalarial derivative with selectivity indexes (SI) of 887.29 on the W2 P. falciparum chloroquine-resistant strain, and of 1035.17 on the chloroquine-sensitive and mefloquine decreased sensitivity strain 3D7. It has been previously described that the telomeres of P. falciparum could represent potential targets for these types of polyaromatic compounds; therefore, the capacity of our novel derivatives to stabilize the parasitic telomeric G-quadruplexes was assessed using a FRET melting assay. However, with regard to the stabilization of the protozoal G-quadruplex, we observed that the best substituted derivatives 1, which exhibited some interesting stabilization profiles, were not the most active antimalarial compounds against the two Plasmodium strains. Thus, there were no correlations between their antimalarial activities and selectivities of their respective binding to G-quadruplexes.

Published
2024
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2. Synthesis and Antimalarial Evaluation of New 1,3,5-tris[(4-(Substituted-aminomethyl)phenyl)methyl]benzene Derivatives: A Novel Alternative Antiparasitic Scaffold

Author

Sandra Albenque-Rubio, Jean Guillon, Anita Cohen, Patrice Agnamey, Solène Savrimoutou, Stéphane Moreau, Jean-Louis Mergny, Luisa Ronga, Ioannis Kanavos, Serge Moukha, Pascale Dozolme, and Pascal Sonnet

Subjects
antimalarial activity, 1,3,5-tris[(4-(substituted-aminomethyl)phenyl)methyl]benzene, antileishmanial activity, Pharmacy and materia medica, RS1-441, Chemistry, QD1-999
Abstract

A series of new 1,3,5-tris[(4-(substituted-aminomethyl)phenyl)methyl]benzene compounds were designed, synthesized, and evaluated in vitro against two parasites (Plasmodium falciparum and Leishmania donovani). The biological results showed antimalarial activity with IC50 values in the sub and μM range. The in vitro cytotoxicity of these new aza polyaromatic derivatives was also evaluated on human HepG2 cells. The 1,3,5-tris[(4-(substituted-aminomethyl)phenyl)methyl]benzene 1m was found as one of the most potent and promising antimalarial candidates with a ratio of cytotoxic to antiprotozoal activities of 83.67 against the P. falciparum CQ-sensitive strain 3D7. In addition, derivative 1r was also identified as the most interesting antimalarial compound with a selectivity index (SI) of 17.28 on the W2 P. falciparum CQ-resistant strain. It was previously described that the telomeres of P. falciparum could be considered as potential targets of these kinds of aza heterocycles; thus, the ability of these new derivatives to stabilize the parasitic telomeric G-quadruplexes was measured through a FRET melting assay.

Published
2023
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3. Design, Synthesis, and Antiprotozoal Evaluation of New Promising 2,9-Bis[(substituted-aminomethyl)]-4,7-phenyl-1,10-phenanthroline Derivatives, a Potential Alternative Scaffold to Drug Efflux

Author

Jean Guillon, Anita Cohen, Clotilde Boudot, Sarah Monic, Solène Savrimoutou, Stéphane Moreau, Sandra Albenque-Rubio, Camille Lafon-Schmaltz, Alexandra Dassonville-Klimpt, Jean-Louis Mergny, Luisa Ronga, Mikel Bernabeu de Maria, Jeremy Lamarche, Cristina Dal Lago, Eric Largy, Valérie Gabelica, Serge Moukha, Pascale Dozolme, Patrice Agnamey, Nadine Azas, Catherine Mullié, Bertrand Courtioux, and Pascal Sonnet

Subjects
antimalarial activity, phenanthroline, G-quadruplex, antileishmanial activity, antitrypanosomal activity, Medicine
Abstract

A series of novel 2,9-bis[(substituted-aminomethyl)]-4,7-phenyl-1,10-phenanthroline derivatives was designed, synthesized, and evaluated in vitro against three protozoan parasites (Plasmodium falciparum, Leishmania donovani and Trypanosoma brucei brucei). Pharmacological results showed antiprotozoal activity with IC50 values in the sub and μM range. In addition, the in vitro cytotoxicity of these original molecules was assessed with human HepG2 cells. The substituted diphenylphenanthroline 1l was identified as the most potent antimalarial derivative with a ratio of cytotoxic to antiparasitic activities of 505.7 against the P. falciparum CQ-resistant strain W2. Against the promastigote forms of L. donovani, the phenanthrolines 1h, 1j, 1n and 1o were the most active with IC50 from 2.52 to 4.50 μM. The phenanthroline derivative 1o was also identified as the most potent trypanosomal candidate with a selectivity index (SI) of 91 on T. brucei brucei strain. FRET melting and native mass spectrometry experiments evidenced that the nitrogen heterocyclic derivatives bind the telomeric G-quadruplexes of P. falciparum and Trypanosoma. Moreover, as the telomeres of the parasites P. falciparum and Trypanosoma could be considered to be possible targets of this kind of nitrogen heterocyclic derivatives, their potential ability to stabilize the parasitic telomeric G-quadruplexes have been determined through the FRET melting assay and by native mass spectrometry.

Published
2022
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4. Synthesis and Antiprotozoal Evaluation of New 2,9-bis[(pyridinylalkylaminomethyl) phenyl]-1,10-Phenanthroline Derivatives by Targeting G-quadruplex, an Interesting Pharmacophore Against Drug Efflux

Author

Jean Guillon, Anita Cohen, Sarah Monic, Clotilde Boudot, Solène Savrimoutou, Sandra Albenque-Rubio, Stéphane Moreau, Alexandra Dassonville-Klimpt, Jean-Louis Mergny, Luisa Ronga, Mikel Bernabeu de Maria, Nikita Tyurin-Schmitt, Paul Parrens, Adrien Labarthe, Valentin Gomez, Serge Moukha, Pascale Dozolme, Nadine Azas, Valérie Gabelica, Patrice Agnamey, Céline Damiani, Anne Totet, Catherine Mullié, Bertrand Courtioux, and Pascal Sonnet

Subjects
General Materials Science
Published
2023
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6. Design, Synthesis, and Antiprotozoal Evaluation of New Promising 2,9-Bis[(substituted-aminomethyl)]-4,7-phenyl-1,10phenanthroline Derivatives, a Potential Alternative Scaffold to Drug Efflux

Author

Jean Guillon, Anita Cohen, Clotilde Boudot, Sarah Monic, Solène Savrimoutou, Stéphane Moreau, Sandra Albenque-Rubio, Camille Lafon-Schmaltz, Alexandra Dassonville-Klimpt, Jean-Louis Mergny, Luisa Ronga, Mikel Bernabeu de Maria, Jeremy Lamarche, Cristina Dal Lago, Eric Largy, Valérie Gabelica, Serge Moukha, Pascale Dozolme, Patrice Agnamey, Nadine Azas, Catherine Mullié, Bertrand Courtioux, Pascal Sonnet, Acides Nucléiques : Régulations Naturelle et Artificielle (ARNA), Université de Bordeaux (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Vecteurs - Infections tropicales et méditerranéennes (VITROME), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut de Recherche Biomédicale des Armées (IRBA), Neuroépidémiologie Tropicale (NET), CHU Limoges-Institut d'Epidémiologie Neurologique et de Neurologie Tropicale-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST), Université de Limoges (UNILIM)-Université de Limoges (UNILIM), Agents infectieux, résistance et chimiothérapie - UR UPJV 4294 (AGIR ), Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie, Laboratoire d'Optique et Biosciences (LOB), École polytechnique (X)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut Polytechnique de Paris (IP Paris), Institut des sciences analytiques et de physico-chimie pour l'environnement et les materiaux (IPREM), Université de Pau et des Pays de l'Adour (UPPA)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Environnement, Santé/Stic (E2S), Université de Bourgogne (UB), Université de Pau et des Pays de l'Adour (UPPA), Institut Européen de Chimie et Biologie (IECB), Université de Bordeaux (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre de recherche Cardio-Thoracique de Bordeaux [Bordeaux] (CRCTB), Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux]-Institut National de la Santé et de la Recherche Médicale (INSERM), Mergny, Jean-Louis, Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut de Recherche Biomédicale des Armées [Brétigny-sur-Orge] (IRBA), Unité de recherche Mycologie et Sécurité des Aliments (MycSA), and Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)

Subjects
Microbiology (medical), General Immunology and Microbiology, G-quadruplex, antimalarial activity, phenanthroline, antileishmanial activity, antitrypanosomal activity, [SDV.BBM.BP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biophysics, [SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], [SDV.BBM.BP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biophysics, Infectious Diseases, [SDV.BC.BC] Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], Immunology and Allergy, [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM], Molecular Biology, [SDV.BBM.BC] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM]
Abstract

International audience; A series of novel 2,9-bis[(substituted-aminomethyl)]-4,7-phenyl-1,10-phenanthroline derivatives was designed, synthesized, and evaluated in vitro against three protozoan parasites (Plasmodium falciparum, Leishmania donovani and Trypanosoma brucei brucei). Pharmacological results showed antiprotozoal activity with IC50 values in the sub and μM range. In addition, the in vitro cytotoxicity of these original molecules was assessed with human HepG2 cells. The substituted diphenylphenanthroline 1l was identified as the most potent antimalarial derivative with a ratio of cytotoxic to antiparasitic activities of 505.7 against the P. falciparum CQ-resistant strain W2. Against the promastigote forms of L. donovani, the phenanthrolines 1h, 1j, 1n and 1o were the most active with IC50 from 2.52 to 4.50 μM. The phenanthroline derivative 1o was also identified as the most potent trypanosomal candidate with a selectivity index (SI) of 91 on T. brucei brucei strain. FRET melting and native mass spectrometry experiments evidenced that the nitrogen heterocyclic derivatives bind the telomeric G-quadruplexes of P. falciparum and Trypanosoma. Moreover, as the telomeres of the parasites P. falciparum and Trypanosoma could be considered to be possible targets of this kind of nitrogen heterocyclic derivatives, their potential ability to stabilize the parasitic telomeric G-quadruplexes have been determined through the FRET melting assay and by native mass spectrometry.

Published
2022
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7. Design, synthesis, and characterization of novel aminoalcohol quinolines with strong in vitro antimalarial activity

Author

Catherine Mullié, Mathieu Marchivie, Patrice Agnamey, Anne Totet, Bruno Pradines, Anita Cohen, Alexandra Dassonville-Klimpt, Jérôme Dormoi, Jean Guillon, Nadine Azas, Céline Damiani, Pascal Sonnet, Jeremy Schneider, N. Taudon, C. Tisnerat, Toulin, Stéphane, Agents infectieux, résistance et chimiothérapie - UR UPJV 4294 (AGIR ), Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie, Vecteurs - Infections tropicales et méditerranéennes (VITROME), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut de Recherche Biomédicale des Armées (IRBA), Institut de Chimie de la Matière Condensée de Bordeaux (ICMCB), Université de Bordeaux (UB)-Institut Polytechnique de Bordeaux-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Acides Nucléiques : Régulations Naturelle et Artificielle (ARNA), Université de Bordeaux (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Institut de Recherche Biomédicale des Armées (IRBA), Institut Hospitalier Universitaire Méditerranée Infection (IHU Marseille), Centre National de Référence du Paludisme [IRBA, Marseille] (CNRP), Institut de Recherche Biomédicale des Armées [Antenne Marseille] (IRBA)-Institut Hospitalier Universitaire Méditerranée Infection (IHU Marseille), The authors would like to thank Philippe Grellier, department RDDM at Muséum National d’Histoire Naturelle (Paris, France), for providing generously the 3D7 and W2 P. falciparum strains and Sylvie Klieber and Alain Pellet, Sanofi R et D France, for in vitro ADMET study (Papp, hERG activity, microsomal and hepatic clearance and CY3A4 activity)., Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut de Recherche Biomédicale des Armées [Brétigny-sur-Orge] (IRBA), Institut de Recherche Biomédicale des Armées [Brétigny-sur-Orge] (IRBA), and ANR-21-ASM1-0003,MORHOC'H 2,Modélisation de l'interaction de la houle et d'un courant inhomogène en zone côtière(2021)

Subjects
Plasmodium falciparum, P. falciparum, mefloquine analogs, Cell Line, 03 medical and health sciences, Antimalarials, Mice, Structure-Activity Relationship, Cricetulus, Pharmacokinetics, Parasitic Sensitivity Tests, In vivo, Drug Discovery, Ic50 values, Animals, Humans, antimalarial drug resistance, aminoalcohol quinolines, 030304 developmental biology, Pharmacology, 0303 health sciences, Mice, Inbred BALB C, [CHIM.MATE] Chemical Sciences/Material chemistry, Dose-Response Relationship, Drug, Molecular Structure, 030306 microbiology, Chemistry, Organic Chemistry, General Medicine, [CHIM.MATE]Chemical Sciences/Material chemistry, Combinatorial chemistry, Amino Alcohols, In vitro, Ether-A-Go-Go Potassium Channels, 3. Good health, Malaria, Design synthesis, Novel agents, Drug Design, Microsomes, Liver, Quinolines, Female, Selectivity
Abstract

International audience; Malaria is the fifth most lethal parasitic infections in the world. Herein, five new series of aminoalcohol quinolines including fifty-two compounds were designed, synthesized and evaluated in vitro against Pf3D7 and PfW2 strains. Among them, fourteen displayed IC50 values below or near of 50.0 nM whatever the strain with selectivity index often superior to 100. 17b was found as a promising antimalarial candidate with IC50 values of 14.9 nM and 11.0 nM against respectively Pf3D7 and PfW2 and a selectivity index higher than 770 whatever the cell line is. Further experiments were achieved to confirm the safety and to establish the preliminary ADMET profile of compound 17b before the in vivo study performed on a mouse model of P. berghei ANKA infection. The overall data of this study allowed to establish new structure-activity relationships and the development of novel agents with improved pharmacokinetic properties

Published
2022
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