Synthesis, biological evaluation and molecular modeling studies of quinolonyl diketo acid derivatives: New structural insight into the HIV-1 integrase inhibition

Pierre Vandurm, Allan Guiguen, Christine Cauvin, Benoît Georges, Kiet Le Van, Catherine Michaux, Christelle Cardona, Gladys Mbemba, Jean Franois Mouscadet, Laszlo Hevesi, Carine Van Lint, Johan Wouters

Research output: Contribution to journalArticle

Abstract

New quinolonyl diketo acid compounds bearing various substituents at position 6 of the quinolone scaffold were designed and synthesized as potential HIV-1 integrase inhibitors. These new compounds were evaluated for their antiviral and anti-integrase activity and showed inhibitory potency similar to that of 6-bromide analog 2. Molecular modeling and docking studies were performed to rationalize these data and to provide a detailed understanding of the mechanism of inhibition for this class of compounds.

Original languageEnglish
Pages (from-to)1749-1756
Number of pages8
JournalEuropean Journal of Medicinal Chemistry
Volume46
Issue number5
DOIs
Publication statusPublished - 1 May 2011

Fingerprint

Bearings (structural)
HIV Integrase Inhibitors
Integrase Inhibitors
Integrases
Molecular modeling
Quinolones
Bromides
Scaffolds
Antiviral Agents
Derivatives
Acids
p31 integrase protein, Human immunodeficiency virus 1

Keywords

  • Anti-integrase activity
  • Antiviral activity
  • Docking
  • HIV-1 IN
  • Molecular modeling
  • Quinolonyl diketo acid

Cite this

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abstract = "New quinolonyl diketo acid compounds bearing various substituents at position 6 of the quinolone scaffold were designed and synthesized as potential HIV-1 integrase inhibitors. These new compounds were evaluated for their antiviral and anti-integrase activity and showed inhibitory potency similar to that of 6-bromide analog 2. Molecular modeling and docking studies were performed to rationalize these data and to provide a detailed understanding of the mechanism of inhibition for this class of compounds.",
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AU - Vandurm, Pierre

AU - Guiguen, Allan

AU - Cauvin, Christine

AU - Georges, Benoît

AU - Le Van, Kiet

AU - Michaux, Catherine

AU - Cardona, Christelle

AU - Mbemba, Gladys

AU - Mouscadet, Jean Franois

AU - Hevesi, Laszlo

AU - Van Lint, Carine

AU - Wouters, Johan

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