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 journalArticle

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

Fingerprint

HIV Integrase Inhibitors
Integrase Inhibitors
Quinolones
Dihedral angle
Structure-Activity Relationship
X-Ray Diffraction
Antiviral Agents
Esters
Theoretical Models
X ray diffraction
Acids
p31 integrase protein, Human immunodeficiency virus 1

Keywords

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

Cite this

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title = "Structural and theoretical studies of [6-bromo-1-(4-fluorophenylmethyl)-4(1H)-quinolinon-3-yl)]-4-hydroxy-2-oxo-3-buteno{\"i}c acid as HIV-1 integrase inhibitor",
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-buteno{\"i}c 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.",
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author = "Pierre Vandurm and Christine Cauvin and Allan Guiguen and Beno{\^i}t Georges and Van, {Kiet Le} and Val{\'e}rie Martinelli and Christelle Cardona and Gladys Mbemba and Mouscadet, {Jean Fran{\cc}ois} and L{\'a}szl{\'o} Hevesi and Lint, {Carine Van} and Johan Wouters",
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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. / Vandurm, Pierre; Cauvin, Christine; Guiguen, Allan; Georges, Benoît; Van, Kiet Le; Martinelli, Valérie; Cardona, Christelle; Mbemba, Gladys; Mouscadet, Jean François; Hevesi, László; Lint, Carine Van; Wouters, Johan.

In: Bioorganic & Medicinal Chemistry Letters, Vol. 19, No. 16, 15.08.2009, p. 4806-4809.

Research output: Contribution to journalArticle

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AU - Vandurm, Pierre

AU - Cauvin, Christine

AU - Guiguen, Allan

AU - Georges, Benoît

AU - Van, Kiet Le

AU - Martinelli, Valérie

AU - Cardona, Christelle

AU - Mbemba, Gladys

AU - Mouscadet, Jean François

AU - Hevesi, László

AU - Lint, Carine Van

AU - Wouters, Johan

PY - 2009/8/15

Y1 - 2009/8/15

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