Identification and structure-activity relationship of 8-hydroxy-quinoline-7-carboxylic acid derivatives as inhibitors of Pim-1 kinase

Faten Sliman; Mélina Blairvacq; Emilie Durieu; Laurent Meijer; Jordi Rodrigo; Didier Desmaële

doi:10.1016/j.bmcl.2010.03.061

Identification and structure-activity relationship of 8-hydroxy-quinoline-7-carboxylic acid derivatives as inhibitors of Pim-1 kinase

Bioorg Med Chem Lett. 2010 May 1;20(9):2801-5. doi: 10.1016/j.bmcl.2010.03.061. Epub 2010 Mar 15.

Authors

Faten Sliman¹, Mélina Blairvacq, Emilie Durieu, Laurent Meijer, Jordi Rodrigo, Didier Desmaële

Affiliation

¹ UMR 89076 BIOCIS, Faculté de Pharmacie, Université Paris Sud, 5 rue J.-B. Clément, 92296 Châtenay-Malabry, France.

PMID: 20363627
DOI: 10.1016/j.bmcl.2010.03.061

Abstract

Pim-1 kinase is a cytoplasmic serine/threonine kinase that controls programmed cell death by phosphorylating substrates that regulate both apoptosis and cellular metabolism. A series of 2-styrylquinolines and quinoline-2-carboxamides has been identified as potent inhibitors of the Pim-1 kinase. The 8-hydroxy-quinoline 7-carboxylic acid moiety appeared to be a crucial pharmacophore for activity. Molecular modeling indicated that interaction of this scaffold with Asp186 and Lys67 residues within the ATP-binding pocket might be responsible for the kinase inhibitory potency.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Antineoplastic Agents / chemical synthesis
Antineoplastic Agents / chemistry*
Antineoplastic Agents / pharmacology
Binding Sites
Computer Simulation
Protein Kinase Inhibitors / chemical synthesis
Protein Kinase Inhibitors / chemistry*
Protein Kinase Inhibitors / pharmacology
Proto-Oncogene Proteins c-pim-1 / antagonists & inhibitors*
Proto-Oncogene Proteins c-pim-1 / metabolism
Quinolines / chemical synthesis
Quinolines / chemistry*
Quinolines / pharmacology
Structure-Activity Relationship

Substances

Antineoplastic Agents
Protein Kinase Inhibitors
Quinolines
Proto-Oncogene Proteins c-pim-1