Synthesis, Pim kinase inhibitory potencies and in vitro antiproliferative activities of diversely substituted pyrrolo[2,3-a]carbazoles

Rufine Akué-Gédu (1) , Lionel Nauton (1) , Vincent Thery (1) , Jenny Bain , Philip Cohen (2) , Fabrice Anizon (1) , Pascale Moreau (1)

1 SEESIB - Synthèse et étude de systèmes à intêret biologique
2 MRC Protein Phosphorylation Unit

The synthesis of new pyrrolo[2,3-a]carbazole derivatives diversely substituted at the C-6 to C-9 positions is described. These compounds were tested for their kinase inhibitory potencies toward three kinases (Pim-1, Pim-2, Pim-3) as well as for their in vitro antiproliferative activities toward a human fibroblast primary culture and three human solid cancer cell lines (PC3, DU145, and PA 1). Moreover, molecular docking studies were performed to explain the enhanced inhibitory activity of the most active compound 3d.

Mots clés: Pyrrolo[2; 3-a]carbazoles; Kinase inhibitors; PIM inhibitors; In vitro antiproliferative activities

Rufine Akué-Gédu, Lionel Nauton, Vincent Thery, Jenny Bain, Philip Cohen, et al.. Synthesis, Pim kinase inhibitory potencies and in vitro antiproliferative activities of diversely substituted pyrrolo[2,3-a]carbazoles. Bioorganic and Medicinal Chemistry, 2010, 18, pp.6865-6873. ⟨hal-00530591⟩