X-ray and molecular modelling in fragment-based design of three small quinoline scaffolds for HIV integrase inhibitors

Bioorg Med Chem. 2011 Mar 1;19(5):1606-12. doi: 10.1016/j.bmc.2011.01.045. Epub 2011 Jan 27.

Abstract

Crystal structures of three small molecular scaffolds based on quinoline, 2-methylquinoline-5,8-dione, 5-hydroxy-quinaldine-6-carboxylic acid and 8-hydroxy-quinaldine-7-carboxylic acid, were characterised. 5-Hydroxy-quinaldine-6-carboxylic acid was co-crystallized with cobalt(II) chloride to form a model of divalent metal cation-ligand interactions for potential HIV integrase inhibitors. Molecular docking into active site of HIV IN was also performed on 1WKN PDB file. Selected ligand-protein interactions have been found specific for active compounds. Studied structures can be used as scaffolds in fragment-based design of new potent drugs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Catalytic Domain
  • Crystallography, X-Ray
  • Drug Design
  • HIV Integrase / metabolism*
  • HIV Integrase Inhibitors* / chemistry
  • HIV Integrase Inhibitors* / pharmacology
  • HIV-1 / drug effects*
  • Inhibitory Concentration 50
  • Ligands
  • Models, Molecular*
  • Molecular Structure
  • Quinolines / chemical synthesis*
  • Quinolines / chemistry*
  • Quinolines / pharmacology

Substances

  • HIV Integrase Inhibitors
  • Ligands
  • Quinolines
  • quinoline
  • HIV Integrase