title: Design, synthesis and biological evaluation of novel 4-alkapolyenylpyrrolo[1,2-a]quinoxalines as antileishmanial agents--part III.
abstract: A series of new 4-alkapolyenylpyrrolo[1,2-a]quinoxaline derivatives, original and structural analogues of alkaloid chimanine B and of previously described 4-alkenylpyrrolo[1,2-a]quinoxalines, was synthesized in good yields using efficient palladium-catalyzed Suzuki-Miyaura cross-coupling reactions. These new compounds were tested for in vitro antiparasitic activity upon three Leishmania spp. strains. Biological results showed activity against the promastigote forms of L. major, L. mexicana and L. donovani with IC50 ranging from 1.2 to 14.7 μM. In attempting to investigate if our pyrrolo[1,2-a]quinoxaline derivatives are broad-spectrum antiprotozoal compounds activities toward one Trypanosoma brucei brucei strain and the W2 and 3D7 Plasmodium falciparum strains were also investigated. In parallel, the in vitro cytotoxicity of these molecules was assessed on the murine J774 and human HepG2 cell lines. Structure-activity relationships of these new synthetic compounds are here discussed.
authors.affiliation: Univ. Bordeaux, UFR des Sciences Pharmaceutiques, ARNA Laboratory, F-33076 Bordeaux Cedex, France; INSERM U869, ARNA Laboratory, F-33000 Bordeaux, France.
authors.forename: Luisa
authors.initials: L
authors.lastname: Ronga
authors.affiliation: Univ. Bordeaux, UFR des Sciences Pharmaceutiques, ARNA Laboratory, F-33076 Bordeaux Cedex, France; INSERM U869, ARNA Laboratory, F-33000 Bordeaux, France.
authors.forename: Marco
authors.initials: M
authors.lastname: Del Favero
authors.affiliation: Aix-Marseille Univ., Laboratory of Parasitology, UMR-MD3, Faculty of Pharmacy, 27 Bd Jean Moulin, CS30064, F-13385 Marseille Cedex 5, France.
authors.forename: Anita
authors.initials: A
authors.lastname: Cohen
authors.affiliation: Univ. Bordeaux, UFR des Sciences Pharmaceutiques, ARNA Laboratory, F-33076 Bordeaux Cedex, France; INSERM U869, ARNA Laboratory, F-33000 Bordeaux, France.
authors.forename: Claire
authors.initials: C
authors.lastname: Soum
authors.affiliation: Université de Nantes, Département de Parasitologie et Mycologie Médicale, IICiMed, EA1155, UFR des Sciences Pharmaceutiques, F-44000 Nantes, France.
authors.forename: Patrice
authors.initials: P
authors.lastname: Le Pape
authors.affiliation: Univ. Bordeaux, UFR des Sciences Pharmaceutiques, ARNA Laboratory, F-33076 Bordeaux Cedex, France; INSERM U869, ARNA Laboratory, F-33000 Bordeaux, France.
authors.forename: Solène
authors.initials: S
authors.lastname: Savrimoutou
authors.affiliation: Univ. Bordeaux, ISM - CNRS UMR 5255, 351 cours de la Libération, F-33405 Talence Cedex, France.
authors.forename: Noël
authors.initials: N
authors.lastname: Pinaud
authors.affiliation: Université de Picardie Jules Verne, Laboratoire de Glycochimie, des Antimicrobiens et des Agroressouces, CNRS FRE 3517, UFR de Pharmacie, 1 Rue des Louvels, F-80037 Amiens Cedex 01, France.
authors.forename: Catherine
authors.initials: C
authors.lastname: Mullié
authors.affiliation: UMR 177 IRD CIRAD, Université de Bordeaux, Laboratoire de Parasitologie, F-33076 Bordeaux Cedex, France.
authors.forename: Sylvie
authors.initials: S
authors.lastname: Daulouede
authors.affiliation: UMR 177 IRD CIRAD, Université de Bordeaux, Laboratoire de Parasitologie, F-33076 Bordeaux Cedex, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Vincendeau
authors.affiliation: Université de Picardie Jules Verne, Laboratoire de Glycochimie, des Antimicrobiens et des Agroressouces, CNRS FRE 3517, UFR de Pharmacie, 1 Rue des Louvels, F-80037 Amiens Cedex 01, France.
authors.forename: Natacha
authors.initials: N
authors.lastname: Farvacques
authors.affiliation: Université de Picardie Jules Verne, Laboratoire de Glycochimie, des Antimicrobiens et des Agroressouces, CNRS FRE 3517, UFR de Pharmacie, 1 Rue des Louvels, F-80037 Amiens Cedex 01, France; CHU Amiens, Laboratoire de Parasitologie-Mycologie, Avenue Laënnec, 80054 Amiens, France.
authors.forename: Patrice
authors.initials: P
authors.lastname: Agnamey
authors.affiliation: Université de Nantes, Département de Parasitologie et Mycologie Médicale, IICiMed, EA1155, UFR des Sciences Pharmaceutiques, F-44000 Nantes, France.
authors.forename: Fabrice
authors.initials: F
authors.lastname: Pagniez
authors.affiliation: Aix-Marseille Univ., Laboratory of Parasitology, UMR-MD3, Faculty of Pharmacy, 27 Bd Jean Moulin, CS30064, F-13385 Marseille Cedex 5, France.
authors.forename: Sébastien
authors.initials: S
authors.lastname: Hutter
authors.affiliation: Aix-Marseille Univ., Laboratory of Parasitology, UMR-MD3, Faculty of Pharmacy, 27 Bd Jean Moulin, CS30064, F-13385 Marseille Cedex 5, France.
authors.forename: Nadine
authors.initials: N
authors.lastname: Azas
authors.affiliation: Université de Picardie Jules Verne, Laboratoire de Glycochimie, des Antimicrobiens et des Agroressouces, CNRS FRE 3517, UFR de Pharmacie, 1 Rue des Louvels, F-80037 Amiens Cedex 01, France.
authors.forename: Pascal
authors.initials: P
authors.lastname: Sonnet
authors.affiliation: Univ. Bordeaux, UFR des Sciences Pharmaceutiques, ARNA Laboratory, F-33076 Bordeaux Cedex, France; INSERM U869, ARNA Laboratory, F-33000 Bordeaux, France. Electronic address: jean.guillon@u-bordeaux.fr.
authors.forename: Jean
authors.initials: J
authors.lastname: Guillon
mesh_terms: D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D005260:Female; D056945:Hep G2 Cells; D006801:Humans; D007891:Leishmania / Q000187:drug effects*; D008264:Macrophages / Q000187:drug effects; D051379:Mice; D015394:Molecular Structure; D021261:Parasitic Sensitivity Tests; D010963:Plasmodium falciparum / Q000187:drug effects*; D011810:Quinoxalines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014344:Trypanocidal Agents / Q000008:administration & dosage / Q000138:chemical synthesis / Q000494:pharmacology*; D014346:Trypanosoma brucei brucei / Q000187:drug effects*; D014353:Trypanosomiasis, African / Q000188:drug therapy* / Q000469:parasitology / Q000662:veterinary
chemical_list: D011810:Quinoxalines; D014344:Trypanocidal Agents
keywords: Antileishmanial activity; Antimalarial activity; Antitrypanosomal activity; Pyrrolo[1,2-a]quinoxaline; Suzuki reaction; Synthesis