title: Kinase inhibitory potencies and in vitro antiproliferative activities of N-10 substituted pyrrolo[2,3-a]carbazole derivatives.
abstract: Development of potent and selective Pim kinase inhibitors has recently emerged as an important field for the design of new anti-cancer drugs. We report the synthesis of new N-10-substituted pyrrolo[2,3-a]carbazole derivatives and their evaluation as Pim kinase inhibitors. Moreover, in vitro antiproliferative activity of these compounds was evaluated toward a human fibroblast primary culture and three human solid cancer cell lines (PA1, PC3 and DU145). Compounds 3, 7 and 10 showed inhibitory potencies toward Pim-1 and Pim-3 in the nanomolar range. Additionally, dimethylamino analog 10 also demonstrated interesting sub-micromolar antiproliferative activities toward the cell lines tested.
authors.affiliation: Clermont Université, Université Blaise Pascal, Institut de Chimie de Clermont-Ferrand, Clermont-Ferrand, France.
authors.forename: Rufine
authors.initials: R
authors.lastname: Akué-Gédu
authors.forename: Boris
authors.initials: B
authors.lastname: Letribot
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Saugues
authors.forename: Eric
authors.initials: E
authors.lastname: Debiton
authors.forename: Fabrice
authors.initials: F
authors.lastname: Anizon
authors.forename: Pascale
authors.initials: P
authors.lastname: Moreau
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D002227:Carbazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D006801:Humans; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D051573:Proto-Oncogene Proteins c-pim-1 / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D002227:Carbazoles; D047428:Protein Kinase Inhibitors; D051573:Proto-Oncogene Proteins c-pim-1; C406031:proto-oncogene proteins pim