title: Synthesis and activities of new indolopyrrolobenzodiazepine derivatives toward acute myeloid leukemia cells.
abstract: The synthesis of new indolopyrrolobenzodiazepine derivatives is described. Six compounds were selected for evaluation of cytotoxicity towards acute myeloid leukemia (AML) cells and normal fibroblasts. One compound (29) showed selective AML cell death induction. Its action was only partly overcome by knock-down of p53 or Bcl-2 overexpression, suggesting a strong activation of intrinsic apoptotic pathways.
authors.affiliation: Université Clermont Auvergne, Université Blaise Pascal, Institut de Chimie de Clermont-Ferrand, BP 10448, F-63000 Clermont-Ferrand, France; CNRS, UMR 6296, ICCF, F-63178 Aubière, France.
authors.forename: Francis
authors.initials: F
authors.lastname: Giraud
authors.affiliation: Université Clermont Auvergne, Université Blaise Pascal, Institut de Chimie de Clermont-Ferrand, BP 10448, F-63000 Clermont-Ferrand, France; CNRS, UMR 6296, ICCF, F-63178 Aubière, France.
authors.forename: Marion
authors.initials: M
authors.lastname: Bourhis
authors.affiliation: Université Clermont Auvergne, Université Blaise Pascal, Institut de Chimie de Clermont-Ferrand, BP 10448, F-63000 Clermont-Ferrand, France; CNRS, UMR 6296, ICCF, F-63178 Aubière, France.
authors.forename: Edris
authors.initials: E
authors.lastname: Ebrahimi
authors.affiliation: Department of Biomedicine, University of Bergen, Jonas Lies vei 91, N-5009 Bergen, Norway; Department of Clinical Sciences, University of Bergen, PO Box 7804, N-5020 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: Romy Roy
authors.initials: RR
authors.lastname: Choudhury
authors.affiliation: Department of Biomedicine, University of Bergen, Jonas Lies vei 91, N-5009 Bergen, Norway.
authors.forename: Ronja
authors.initials: R
authors.lastname: Bjørnstad
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: Université Clermont Auvergne, Université Blaise Pascal, Institut de Chimie de Clermont-Ferrand, BP 10448, F-63000 Clermont-Ferrand, France; CNRS, UMR 6296, ICCF, F-63178 Aubière, France. Electronic address: Fabrice.ANIZON@univ-bpclermont.fr.
authors.forename: Fabrice
authors.initials: F
authors.lastname: Anizon
authors.affiliation: Université Clermont Auvergne, Université Blaise Pascal, Institut de Chimie de Clermont-Ferrand, BP 10448, F-63000 Clermont-Ferrand, France; CNRS, UMR 6296, ICCF, F-63178 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; D001569:Benzodiazepines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000378:metabolism / Q000473:pathology; 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; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D051573:Proto-Oncogene Proteins c-pim-1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D013329:Structure-Activity Relationship; D016159:Tumor Suppressor Protein p53 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53; D001569:Benzodiazepines; C499249:PIM3 protein, human; D017346:Protein Serine-Threonine Kinases; D051573:Proto-Oncogene Proteins c-pim-1
keywords: Acute myeloid leukemia; Apoptosis; Fibroblasts; Indolopyrrolobenzodiazepine; Pim kinase inhibition