title: New N-1,N-10-bridged pyrrolo[2,3-a]carbazole-3-carbaldehydes: synthesis and biological activities.
abstract: The synthesis of new pyrrolocarbazoles substituted at N-1/N-10 positions is described. All the compounds tested demonstrated moderate to high Pim-1/Pim-3 kinase inhibitory potency. The most active inhibitors identified in this series (3, 17) have an alkyl chain bridging the N-1 and N-10 positions. These compounds (3, 17) exhibited apoptosis-inducing activity toward acute myeloid leukemia IPC-81 cells, but not toward normal fibroblasts.
authors.affiliation: Clermont Université, Université Blaise Pascal, ICCF, BP 10448, 63000 Clermont-Ferrand, France; CNRS, UMR 6296, ICCF, 63177 Aubière, France.
authors.forename: Francis
authors.initials: F
authors.lastname: Giraud
authors.affiliation: Clermont Université, Université Blaise Pascal, ICCF, BP 10448, 63000 Clermont-Ferrand, France; CNRS, UMR 6296, ICCF, 63177 Aubière, France.
authors.forename: Marion
authors.initials: M
authors.lastname: Bourhis
authors.affiliation: Clermont Université, Université Blaise Pascal, ICCF, BP 10448, 63000 Clermont-Ferrand, France; CNRS, UMR 6296, ICCF, 63177 Aubière, France.
authors.forename: Lionel
authors.initials: L
authors.lastname: Nauton
authors.affiliation: Clermont Université, Université Blaise Pascal, ICCF, BP 10448, 63000 Clermont-Ferrand, France; CNRS, UMR 6296, ICCF, 63177 Aubière, France.
authors.forename: Vincent
authors.initials: V
authors.lastname: Théry
authors.affiliation: Department of Biomedicine, University of Bergen, Jonas Lies vei 91, N-5009 Bergen, Norway.
authors.forename: Lars
authors.initials: L
authors.lastname: Herfindal
authors.affiliation: Department of Biomedicine, University of Bergen, Jonas Lies vei 91, N-5009 Bergen, Norway.
authors.forename: Stein Ove
authors.initials: SO
authors.lastname: Døskeland
authors.affiliation: Clermont Université, Université Blaise Pascal, ICCF, BP 10448, 63000 Clermont-Ferrand, France; CNRS, UMR 6296, ICCF, 63177 Aubière, France. Electronic address: Fabrice.ANIZON@univ-bpclermont.fr.
authors.forename: Fabrice
authors.initials: F
authors.lastname: Anizon
authors.affiliation: Clermont Université, Université Blaise Pascal, ICCF, BP 10448, 63000 Clermont-Ferrand, France; CNRS, UMR 6296, ICCF, 63177 Aubière, France. Electronic address: Pascale.MOREAU@univ-bpclermont.fr.
authors.forename: Pascale
authors.initials: P
authors.lastname: Moreau
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D002227:Carbazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D045744:Cell Line, Tumor; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000201:enzymology; D062105:Molecular Docking Simulation; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D051573:Proto-Oncogene Proteins c-pim-1 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011758:Pyrroles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D002227:Carbazoles; D047428:Protein Kinase Inhibitors; D011518:Proto-Oncogene Proteins; D011758:Pyrroles; C041514:carbazole; C499249:PIM3 protein, human; D017346:Protein Serine-Threonine Kinases; D051573:Proto-Oncogene Proteins c-pim-1
keywords: Acute myeloid leukemia; Apoptosis; Molecular modeling; Pim kinase inhibition; Pyrrolo[2,3-a]carbazole-3-carbaldehyde