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Recherche Des Molécules Antiparasitaires À L'interface De L'ethnopharmacologie, Des Sciences Analytiques Et De La Biol

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Recherche Des Molécules Antiparasitaires À L'interface De L'ethnopharmacologie, Des Sciences Analytiques Et De La Biol Recherche des molécules antiparasitaires à l’interface de l’ethnopharmacologie, des sciences analytiques et de la biologie Pedro Vasquez Ocmin To cite this version: Pedro Vasquez Ocmin. Recherche des molécules antiparasitaires à l’interface de l’ethnopharmacologie, des sciences analytiques et de la biologie. Chimie thérapeutique. Université Paris-Saclay, 2018. Français. NNT : 2018SACLS479. tel-02153075 HAL Id: tel-02153075 https://tel.archives-ouvertes.fr/tel-02153075 Submitted on 12 Jun 2019 HAL is a multi-disciplinary open access L’archive ouverte pluridisciplinaire HAL, est archive for the deposit and dissemination of sci- destinée au dépôt et à la diffusion de documents entific research documents, whether they are pub- scientifiques de niveau recherche, publiés ou non, lished or not. The documents may come from émanant des établissements d’enseignement et de teaching and research institutions in France or recherche français ou étrangers, des laboratoires abroad, or from public or private research centers. publics ou privés. Recherche des molécules antiparasitaires à l’interface de l’ethnopharmacologie, des sciences : 2018SACLS479 NNT analytiques et de la biologie Thèse de doctorat de l'Université Paris-Saclay préparée à Nom de l’Université Paris Sud École doctorale n°569 : Innovation thérapeutique : du fondamental à l'appliqué (ITFA) Spécialité de doctorat: Chimie Pharmaceutique Thèse présentée par Pedro Gilberto VASQUEZ OCMIN Composition du Jury : Mme. Joëlle Quetin-Leclercq Professeurs, Université catholique de Louvain Rapporteur Mme. Elisabeth Davioud-Charvet Directeur de Recherche, Centre National de Recherche Scientifique Rapporteur M. Philippe Loiseau Professeur, Université Paris Sud Président Mme. Sabrina Boutefnouchet Maître de Conférences, Université Paris Descartes Examinateur M. Michel Sauvain Directeur de Recherche, Institut de Recherche pour le Développement Invité M. Bruno Figadère Directeur de Recherche, Centre National de Recherche Scientifique Directeur de thèse M. Alexandre Maciuk Maître de Conférences, Université Paris Sud Co-Directeur de thèse Université Paris-Saclay Espace Technologique / Immeuble Discovery Route de l’Orme aux Merisiers RD 128 / 91190 Saint-Aubin, France Remerciements -Je tiens à remercier le Professeur Joëlle Quetin-Leclercq et le Docteur Elisabeth Davioud- Charvet pour avoir accepté d’être les rapportrices de ce travail ainsi que le Professeur Philippe Loiseau et les Docteurs Sabrina Boutefnouchet et Michel Sauvain pour avoir accepté d’évaluer ce travail en temps qu’examinateurs. - Je tiens à remercier les institutions : Consejo de Ciencia y Tecnología (CONCYTEC) et Fondo de Ciencia y Tecnología (FONDECYT), pour le financement obtenu pendant ces trois années de thèse. -Je tiens remercie également à la Fédération National des producteurs de Chanvre (FNPC) pour le support financier pour ces 6 derniers mois de thèse. -Ce projet de thèse a été encadré pour le Dr. Alexandre Maciuk et le Dr. Bruno Figadère et s’est déroulé dans l’Equipe de chimie de substances naturelles et antiparasitaires, BioCIS-UMR 8076, Faculté de Pharmacie – Université Paris Sud. -Je tiens à remercier le Dr. Bruno Figadère, Directeur de Recherche de l’UMR-CNRS 8076, pour m’accueillir au sein du laboratoire BIOCIS et ses conseils comme directeur de cette thèse. -Je remercie chaleureusement le Dr. Alexandre Maciuk, directeur de ma thèse, pour ses conseils et sa confiance, pour les heures passées à discuter sur ce projet (l’hème, LCMS, l’ethnopharmacologie, la RMN, etc…) et autres (la vie, la religion, le futur…). Tu m’as toujours donné beaucoup de liberté et aussi des responsabilités pendant ma thèse. Tu as toujours été intéressé et disponible malgré tes responsabilités croissantes. Je suis profondément touché par ta passion à vivre la paternité et l’amour que tu donnes à tes enfants. -Le chemin depuis la 4ème année de Pharmacie jusqu’ici a été super long, donc je vais essayer de le résumer en quelques lignes envers les chercheurs qui m’ont beaucoup appris et je suis plus que reconnaissant. Tout d’abord, merci au Dr. José Betancourt (décédé en 2007) pour me faire découvrir la recherche et au Q.F. Ernesto Nina pour me faire découvrir la chimie des Substances Naturelles (pendant mes années à l’IMET-Iquitos). Merci au Dr. Carmen Rosa Garcia (IIIAP) pour sa gentillesse et pour me montrer sa vision sur la recherche qui continue de me marquer encore aujourd’hui. Merci au Dr. Mohamed Haddad (IRD) pour croire en mes capacités dans la recherche et pour m’avoir aidé à un moment précis. Merci au Dr. Michel Sauvain (IRD) pour m’accueillir au laboratoire à Lima et pour son support financier pendant et 1 après le master. Encore merci au Dr. Michel Sauvain et aussi au Professeur Pierre Champy (Faculté de Pharmacie, Université Paris Sud) pour être les initiateurs de mon arrivée dans l’Equipe de chimie de substances naturelles à Châtenay-Malabry. -Je tiens remercier encore le Dr. Mohamed Haddad et le Dr. Michel Sauvain pour leur aide et leurs conseils dans mes débuts dans la recherche. Vous êtes deux personnes grâce à qui de nombreux étudiants, dont je fais partis, ont eu l’opportunité de découvrir la chimie des substances naturelles. -A Bono, pour les discutions, la musique, les bières et la couleur. -Aux étudiants de l’équipe BIOCIS qui son passés et qui sont encore là, du 3ème étage (Natacha, Alexander, Long, Elvis, Charlotte, Hazrina, Dibi, Aminata), du 4ème (Sigura, Lin, Xinming, Victor) et du 5ème (Anne-Cécile, Katia, Oumayma). Je garderai toujours de bons souvenirs des choses vécues avec vous, comme les déjeuners au resto universitaire, quelques sorties hors du labo et surtout les mélanges de cultures. -Je tiens remercier les permanents de l’équipe de BIOCIS: Karine, Pierre (x2), Laurent (x2), Blandine, Guillaume, Christophe, Mehdi, Camille, Jocelyne, François, Erwan. -A Karine Le Blanc pour son support LCMS, c’était un vrai plaisir et très enrichissent de discuter avec toi, j’ai beaucoup appris. -A Blandine Séon-Méniel pour être toujours si aimable et souriante dans le laboratoire. Merci aussi pour toutes les commandes des kilos de carboglace pour faire avancer mon projet. -A Laurent Evanno pour ses blagues, ses graphical abstracts « inspirants» et son aide avec la RMN. -A Guillaume Bernadant pour les multiples formations en bioinformatique malgré mes déficiences dans ce domaine. -Aux personnels administratif de BIOCIS : Agnès Rasneur et Nathalie Lemière. Merci pour avoir fait tout votre possible pour prendre en charge mes missions de dernières minutes. -A Soulaf Suyyagh-Albouz et Sandrine Cojean de l’Equipe “Chimiothérapie antiparasitaire”, BIOCIS. Merci beaucoup pour les tests antiplasmodiaux et anti-leishmanioses, avec vous deux j’ai beaucoup appris sur la parasitologie en particuliers sur Plasmodium. -A Sergio Ortiz et Sabrina Boutefnouchet du Laboratoire de Pharmacognosie (UMR CNRS 8638 COMETE) de l’Université Paris Descartes. C’était très enrichissant nos projets et les discussions sur les méthoxyflavones et ses liaisons à cette molécule « rare » appelé l’hème. 2 -A Abdoulaye Sissoko et Romain Duval de l’Unité MERIT-UMR IRD 216 de l’Université Paris Descartes. C’était un vrai plaisir travailler avec vous dans ce projet très enrichissent des sondes d’artémisinine. -A Jean-François Gallard de l’Institut de Chimie de Substances Naturelles, Gif-Sur-Yvette. Merci pour toute sa disponibilité et sa gentillesse lors des analyses RMN de mes composés. -A Carlos Amasifuen pour sa grande aide et sa connaissance sur la botanique des plantes péruviennes. Toujours disponible pour notre travail sur le terrain à Loreto. -A Elisabeth Mouray et Philippe Grellier de l’Unité Molécules de Communication et Adaptation des Microorganismes, UMR 7245, Muséum National d’Histoire Naturelle. Merci pour avoir accepté de tester mes produits sur des souches parasitaires ainsi que pour les tests cytotoxiques. -A Sébastian Pomel et Philipe Loiseau de l’Equipe “Chimiothérapie antiparasitaire” BIOCIS. Merci pour les tests antileishmaniose et anti-trypanosoma. -A Audrey Solgadi de la plateforme SAMM - Service d'Analyse des Médicaments et Métabolites. Merci pour les très enrichissent discussions sur la spectrometrie de masse. -Aux chercheurs de l’Instituto de Investigaciones de la Amazonia Peruana (Iquitos): Elsa Rengifo, Billy Cabanillas, Kember Mejia, Gabriel Arana, Denis del Castillo. -Aux communautés de Métis El Dorado et 13 de Febrero (route Iquitos-Nauta), et les communautés de Lupuna Zona II et Jenaro Herrera en l’Amazonie Péruvienne. Malgré le peu de considération de l’état envers ces communautés, la richesse de leurs connaissances traditionnelles reste intacte. -A Nixen Saavera de la communauté Jenaro Herrera pour son aide dans la collecte des plantes médicinales. -A Agathe Martinez et Jean-Marc Nuzillard de l’Institut de Chimie Moléculaire de Reims de l’Université de Reims Champagne-Ardenne. Merci pour leur aide lors de notre projet LCMS- RMN. -Agradezco a mis amigos peruanos en Francia y España por los momentos de distracción y la amistad constante durante estos casi 4 años de tesis: Juan Pablo, André, Rubi, Lourdes, Jason Marcela y Giovanna. -Agradezco de todo corazón a mi familia (tíos, tías, primos, primas, etc.), en especial a mis padres (Jorge y Martha) y hermanos (Carlos, Jorge, Chaín et Mery Consuelo). 3 -A mi hermano Chaín porque a pesar que eres el menor has sabido crecer rápido y ponerte en la plaza de los mayores. Te tendré siempre una inmensa admiración y respeto por todo lo que haces por la familia. -A mis padres y hermanos, ustedes fueron de una u otra manera un soporte moral desde mis años de estudios en la facultad hasta el término de este proyecto personal, los amo. Después de las innumerables veces que mi padre me preguntó lo mismo, cuando sustentas tu tesis hijo?, hoy puedo responderle: es hoy la sustentación de tesis papá!!! -Je tiens remercier affectueusement à mon autre famille, pour leur aide en France: Jean- Claude, Michèle, Théo, vous êtes des personnes formidables, je vous apprécie beaucoup. -Je remercie vivement à la femme qui a changé ma vie, Alice.
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