Structural and theoretical studies of [6-bromo-1-(4-fluorophenylmethyl)-4(1H)-quinolinon-3-yl)]-4-hydroxy-2-oxo-3-butenoïc acid as HIV-1 integrase inhibitor

Pierre Vandurm, Christine Cauvin, Allan Guiguen, Benoît Georges, Kiet Le Van, Valérie Martinelli, Christelle Cardona, Gladys Mbemba, Jean François Mouscadet, László Hevesi, Carine Van Lint, Johan Wouters

Research output: Contribution to journalArticlepeer-review

Abstract

Ethyl [6-bromo-1-(4-fluorophenylmethyl)-4(1H)-quinolinon-3-yl]-4-hydroxy-2-oxo-3-butenoate 1 and [6-bromo-1-(4-fluorophenylmethyl)-4(1H)-quinolinon-3-yl)]-4-hydroxy-2-oxo-3-butenoïc acid 2 were synthesized as potential HIV-1 integrase inhibitors and evaluated for their enzymatic and antiviral activity, acidic compound 2 being more potent than ester compound 1. X-ray diffraction analyses and theoretical calculations show that the diketoacid chain of compound 2 is preferentially coplanar with the quinolinone ring (dihedral angle of 0-30°). Docking studies suggest binding modes in agreement with structure-activity relationships.

Original languageEnglish
Pages (from-to)4806-4809
Number of pages4
JournalBioorganic & Medicinal Chemistry Letters
Volume19
Issue number16
DOIs
Publication statusPublished - 15 Aug 2009

Keywords

  • β-Diketo
  • HIV-1
  • Integrase inhibitors
  • Quinolinone

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